Recently, nanomedicine have been successfully applied in the cancer therapy. However, how to precisely control the drug release from nanomedicine in tumor tissue and overcome the hypoxic microenvironment of tumor tissue is still an important challenge in the development of nanomedicine. In this work, a new type of drug-loaded nanoparticles P(AAm-co-AN)-AuNRs@CeO2-DOX (PA-DOX) was prepared by combining high-efficiency photothermal reagents, critical up-conversion temperature polymer layer and anti-cancer drug doxorubicin (DOX) for the treatment of liver cancer. In this system, CeO2 can decompose hydrogen peroxide to H2O2 and O2 alleviate the anaerobic microenvironment of liver cancer cells. As a photothermal reagent, AuNRs@CeO2 can convert near-infrared light into heat energy to achieve local heat to kill cancer cells and ablate solid tumors. In addition, the elevated temperature would enable the polymer layer to undergo a phase transition to release more DOX to achieve a controlled release mechanism, which will open up a new horizon for clinical cancer treatment

Report of Two cases of Schaaf-Yang Syndrome: Same Genotype, Different Phenotype Ana Maria Rodriguez,a MD, Katherine Schain,a MS, CGC, Parul Jayakar,aMD,MS,FACMG, Meredith S. Wright,b,c PhD., Shimul Chowdhury,b PhD., Daria Salyakina,ePhD.a Division of Genetics and Metabolism, Nicklaus Children’s Hospital Pediatric Specialists, Miami, (FL,) USA.b Rady Children’s Institute for Genomic Medicine, San Diego, (CA,) USA. c Keck Graduate Institute, Claremont, (CA,) USA. d Personalized Medicine & Health Outcomes Research, Nicklaus Children’s Hospital Pediatric Specialists, Miami, (FL,) USACorresponding Author: Ana Maria Rodriguez BarretoDivision of Genetics and Metabolism, Nicklaus Children’s Hospital Pediatric Specialists, Miami, (FL,). 3100 SW 62nd Avenue, Miami, FL, 33155, USA. Tel: 786-624-4717. Fax : 786-624-4704. E-mail: anamaria.rodriguezbarreto@nicklaushealth.orgCo-authors: Katherine Schain: Katherine.Schain@Nicklaushealth.orgParul Jayakar: Parul.Jayakar@Nicklaushealth.orgMeredith S. Wright: MWright3@rchsd.orgShimul Chowdhury: schowdhury@bluestargenomics.comDaria Salyakina: Daria.Salyakina@Nicklaushealth.orgConflicts of Interests Statement: We know of no conflicts of interests associated with this publication, and there has been no significant financial support for this work that could have influenced its outcome. As Corresponding Author, I confirm that the manuscript has been read and approved for submission by all the named authors.Informed Consent : Written informed consent was obtained from both patients parents.Ethics Declaration: The study was conducted according to the guidelines of the Declaration of Helsinki and approved by The Institutional Review Board (or Ethics Committee) of Nicklaus Children’s Hospital Pediatric Specialists.

Experience of general anesthesia in a patient with menstrual-associated coronary spasmAya Kawachi, Saho Sudo, Yusuke Ishida and Koichi NakazawaDepartment of Anesthesiology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan

Flagella dermatitis is a rare skin lesion due to bleomycin use: A Case ReportZuhat Urakçı1,Yasin Sezgin2,Oğur Karhan3,Suat Morkuzu4,Zeynep Oruç1,Mehmet Küçüköner1,Muhammet Ali Kaplan1,Abdurrahman Işıkdoğan11Dicle University Department of Medical Oncology, Diyarbakir,Turkey2Siirt University, Department of Medical Oncology,Siirt,Turkey3Liv Hospital, Department of Medical Oncology, Gaziantep,Turkey4Institute for Reconstructive Surgery,Houston Methodist Hospital,Houston,Texas,USAAbstract: Flagella dermatitis is a rare skin lesion that appears due to bleomycin use. It is generally seen in itchy and linear styles. Here, we present a case of flagella dermatitis in a male patient who was on bleomycin therapy with a diagnosis of germ cell tumor. When itchy skin lesions develop in patients using bleomycin, it should be kept in mind among the differential diagnoses.Keywords: Flagella dermatitis,bleomycin,germ cell tumor.Introduction: Bleomycin is a glycopeptide-structured cytotoxic drug obtained from Streptomyces verticillus (1). It is often used in the treatment of some malignant tumors, such as Hodgkin lymphoma, squamous cell carcinoma, and germ cell tumors (1). While various side effects occur in the gastrointestinal tract, respiratory system, and skin due to bleomycin, general symptoms such as fever and weakness can also be seen. Skin reactions are common side effects and usually occur as a late finding. On the skin, erythema, hyperkeratosis, rash, vesicle, hyperpigmentation, alopecia, and, in rare cases, Flagella dermatitis (FD) can be seen (2). FD was defined by Moulin et al. in 1970 as linear hyperpigmentation after bleomycin use (1). Its incidence has been reported to be between 8 and 20% in patients using bleomycin (3). Here, a case of FD developed in a 21-year-old male patient using bleomycin due to a germ cell tumor is presented.Case report: A twenty-one-year-old male patient was admitted to our clinic with complaints of shortness of breath and cough that started about 45 days ago. A patient was diagnosed with a mediastinal mass, and a biopsy was performed. The patient, who was reported as a germ cell tumor as a result of a biopsy, was given every 21 days from when bleomycin (30 mg/day, 1, 8 and 15 days), etoposide (100 mg / m2, 1-5 days) and cisplatin (20 mg / m2, 1-5 days), was started. In our patient, hyperpigmented skin lesions that developed with itching, mostly in the chest, abdomen, and back, developed after the 2nd dose of bleomycin (Figure 1.2). Due to the development of the lesions after bleomycin, and in a linear style, FD was considered in our patient. The patient was given oral antihistamine therapy. The dexamethasone that was given before each chemotherapy cycle was continued. During the follow-up, the patient’s itching passed and the skin lesions regressed. The patient’s bleomycin treatment was continued, and there was no itching again.Discussion: The term ”Flagella dermatitis” is used because the hyperpigmented eruptions on the body appear to be whipped (4). In the case of HIV infection, FD may also develop after the consumption of some poisonous mushrooms or after the use of certain chemotherapeutic agents such as peplomycin and docetaxel (5). Bleomycin is an anti-neoplastic drug belonging to the group of glycopeptides, and bleomycin is destroyed by hydrolase. The concentration of the bleomycin hydrolase enzyme is significantly lower in the skin and lungs. Therefore, the accumulation of bleomycin in the skin and lungs is higher and related toxicities develop. Generally, when the cumulative dose reaches 90–285 mg, bleomycin toxicity begins to occur. However, in some cases, it has been reported that toxicity develops at as low as 15 mg intravenously (6). Multiple lesions occur suddenly in many parts of the body. Generally, it develops between the 1st and 9th weeks of bleomycin treatment, but this period may take up to 6 months (7). In our case, FD developed at week 4. Although FD can rarely be asymptomatic, it usually progresses with itching, redness, and darkening of the skin. Indeed, in our case, there was severe itching, redness, and hyperpigmentation of the skin. The diagnosis is made according to the characteristic features of the skin lesions. Linear-style eruptions occur as if they were whipped, characteristically on the skin. The lesions are itchy and usually occur on the upper body and extremities (8). Linear hyperpigmented skin lesions are generally localized in areas where itching and pressure are applied (9). The development mechanism of FD is not known precisely. However, it has been suggested that locally increased melanogenesis, insufficient pigmentation secondary to inflammation, change in normal pigmentation pattern, and neutrophilic eccrine hydradenitis can be caused (10). Patients usually benefit from corticosteroids and anti-histaminics used in treatment. It reduces itching and limits the lesions to the skin. These lesions usually limit themselves after 3-4 months of discontinuation and begin to regress and disappear after 6-8 months. However, after the use of bleomycin again, the lesions may reappear (11). In our case, corticosteroid and anti-histaminic therapy completely alleviated the symptoms.Conclusion: When itchy lesions develop in patients using bleomycin, FD should be kept in mind among the differential diagnoses, and physicians should be careful about the toxicity of bleomycin.Conflict of interest: The authors declared that there is no conflict of interest.

Left ventricular reverse remodeling after annular-mitral valve repair in end-stage heart failure of dilated cardiomyopathy: a case report

Title: AngioinvasiveTrichophyton rubrum associated necrotizing fasciitis in an immunocompromised patientAuthors: Michael J. Davis, DO, MPH1-3*; Katelyn J. Rypka, BS3-6*; Alexandra K. Perron, BA6; John Keilty, BS6; Benjamin Wils, MS 6; Joshua Levine, BA 6; Anthony T. Rezcallah, MD7-8; Robin Solomon, MD9; Noah Goldfarb, MD3-5†; Anjum Kaka, MD1, 3†Affiliations:1Department of Infectious Disease, Minneapolis VA Health Care System, Minneapolis, MN2Department of Infectious Disease, University of Minnesota, Minneapolis, MN3Department of Internal Medicine, Minneapolis VA Health Care System, Minneapolis, MN4Department of Dermatology, Minneapolis VA Health Care System, Minneapolis, MN5Department of Dermatology, University of Minnesota, MN6University of Minnesota Medical School, Minneapolis, MN7Department of Surgery, Minneapolis VA Health Care System, Minneapolis, MN8Department of Surgery, University of Minnesota, Minneapolis, MN9Department of Pathology, Minneapolis VA Health Care System, Minneapolis, MN*These authors contributed equally†These authors contributed equally

TITLE OF CASE Multiple Emergency Department Encounters for Acute Musculoskeletal Presentation with an Existing Mental Health Diagnosis SUMMARY Reconceptualising acute Musculoskeletal (MSK) injuries with both stress- and tissue- based factors is required to consider prior influences of mental health disorders on acute persistent musculoskeletal pain presentations involving an extremity. This report highlights repeated emergency presentations for acute persistent musculoskeletal pain involving an extremity for an individual in their 20s living with mental health diagnoses ranging across Depression, Mood Disorders and an eating disorder. This person also had mental health related inpatient admissions that were not captured under the retrospective record review for a large district hospital emergency department using the Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) classification system. This case report attempts to demonstrate that improving the understanding of pre-existing vulnerabilities and mental health diagnoses may assist with informing healthcare design to develop specialised care pathways for acute injury presentations with triage settings. BACKGROUND Acute MSK pain represents a common cause for seeking emergent health care (1),(2). While the majority of acutely injured people should expect to recover spontaneously, 50% will transition from acute to chronic pain and disability (3, 4). Data from robust clinical trials (5) and prevalence studies have failed to enable us to adequately identify individuals at risk of delayed recovery from MSK injury, and interventions targeting known risk factors have yielded, at best, only modest effects (6, 7). Furthermore, the most recent output from the global burden of disease in 2019 suggest MSK conditions are a leading cause of civilian years lived with disability. Alarmingly, this has not changed since 1990, suggesting research has had little effect on reducing the burdens of acute and chronic MSK conditions. Perhaps critical to this long-standing problem is that research has not generated new mechanistic knowledge into why some people recover and others do not following their acute MSK presentation. (8). Perhaps reconceptualising the acute MSK injury (be it a slip-and-fall, motor vehicle collision, fracture, muscle strain affecting the spine or extremities) as both a stress- and tissue-based injury is required to integrate and consider how pre-existing diatheses such as mental health disorders (9) influence the process of recovery. By identifying patients who may be vulnerable to costly negative chronic outcomes, appropriate early screening tools and preventative treatments can be offered to improve clinical outcomes and avoid harmful secondary effects, such as opioid dependency, stigma, poor return to work outcomes, withdrawal from valued life roles, long-term reliance on ineffective and costly management options and repeat emergency department (ED) encounters. For example, people living with mental health conditions tend to experience adverse physical health outcomes and significantly more medical conditions as compared to others without a history of mental health disorders. This is not to suggest the presence of a mental health disorder(s) predisposes a person to a life of chronic pain following adulthood injury requiring emergent care. While it is acknowledged that the Emergency Department environment presents a challenge, if not a trigger, to both busy, time-strapped, clinicians, and the patients themselves, knowledge of pre-existing diatheses could inform and streamline new clinical pathways for acute MSK injury on a patient-by-patient basis. The case of a Caucasian woman in her twenties seeking repeated ED management over a 7 year period is used to highlight the challenges for both the patient and the healthcare providers in, and beyond, the ED. CASE PRESENTATION The repeated voluntary ED presentations (38 visits over 7 years, from January 2015 – February 2021) were observed to be for persistent musculoskeletal pain, involving an extremity and upper limb pain. Pre-existing diagnoses of Mood Disorder, Depression, and an Eating Disorder (Anorexia Nervosa) were recorded at each ED presentation of persistent MSK pain involving an extremity, and while considered, did not feature in the clinical work-up. The retrospective record review was approved by the Northern Sydney Local Health District Human Research Ethics Committee, ethics approval number – 2021/STE02301: SSA. Design Retrospective interrogation of electronic medical records obtained from January 2015 until July 2021 capturing relevant data for acute presentations of MSK pain intersecting with mental health admissions over the preceding 12-month periods at a district hospital Emergency Department. Setting Emergency department triage facility for a large urban district hospital serving a catchment of over 1.5 million people. Subject A case report of an individual in their twenties, with multiple ED presentations (38 visits) over a 7 year period, classified by the treating ED physician/ clinicians using the SNOMED CT system at each presentation. The SNOMED CT is defined as a standardised, multilingual vocabulary of clinical terminology containing more than 300,000 medical concepts used by health care providers within the electronic exchange of clinical health information (10, 11) . The SNOMED CT is made up of the numerical codes, known as concepts, used to identifying clinical information. The number of concepts used are largely if not completely dependent on the clinical setting and patient census. In this case, the number of concepts available in a busy urban ED with level 1 trauma status is in the thousands. The concepts are divided into different groups such as body structure, clinical findings, geography, location and biological products represented by different concepts based on the complexity of the presenting condition. The terminology classifies presentations under findings, disorders, diagnoses and similar with individual numbers. SNOMED CT classifies “findings” as observations which may be objective or subjective information from a primary source, including human observation whereas the term “disorder” refers to as an abnormal clinical state and are classified under the hierarchy of disease (10). SNOMED CT however also tends to be subjective and have the same description while referring to different concepts due to the ambiguity dependant on the triage (12). The ED admission data captured the date, the patient’s reason for the visit to ED, MSK diagnosis provided at triage, and the pre-existing MH diagnosis. Under SNOMED CT, findings refer to observations that exist at the time of recording, while disorder suggests an abnormal and underlying psycho-physical pathological process that remains a vulnerability even post completion of treatment (11). As summarised in Table 1, the repeated MSK/ acute pain related presentations observed over the 2-year period were for persistent musculoskeletal pain involving an extremity(11). There were multiple mental health related admissions separate to the acute MSK pain presentation at ED over this period recorded initially for an unspecified mood (affective) disorder, progressing to Dysthymia/ Mood Disorder, followed by a separate admission for Post-traumatic stress disorder (PTSD), a further mental health admission for Dissociative convulsions, and the last captured admission was for Anorexia Nervosa (classified under Eating Disorder/s). Information regarding social circumstances, such as living independently or in supported accommodation, employment or education status, social supports both informal and formal including community mental health services, General Practitioner and any non-governmental organisations involvement was not available.

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune condition marked by isolated thrombocytopenia, which makes people more likely to hemorrhage. We provide a case of a 45-year-old female patient with ITP who displayed unusual clinical symptoms, emphasizing the diagnostic difficulties and treatment options in such circumstances.

In root-nodule symbioses (RNS) between nitrogen (N) fixing bacteria and plants, bacterial symbionts cycle between nodule-inhabiting and soil-inhabiting niches that exert differential selection pressures on bacterial traits. Little is known about how the resulting evolutionary tension between host plants and symbiotic bacteria structures naturally occurring bacterial assemblages in soils. We used DNA cloning to examine soil-dwelling assemblages of the actinorhizal symbiont Frankia in sites with long-term stable assemblages in Alnus incana ssp. tenuifolia nodules. We compared: 1) phylogenetic diversity of Frankia in soil vs. nodules, 2) change in Frankia assemblages in soil vs. nodules in response to environmental variation: both across succession, and in response to long-term fertilization with N and phosphorus, and 3) soil assemblages in the presence and absence of host plants. Phylogenetic diversity was much greater in soil-dwelling than nodule-dwelling assemblages, and fell into two large clades not previously observed. Presence of host plants was associated with enhanced representation of genotypes specific to A. tenuifolia, and decreased representation of genotypes specific to a second Alnus species. The relative proportion of symbiotic sequence groups across a primary chronosequence was similar in both soil and nodule assemblages. Contrary to expectations, both N and P enhanced symbiotic genotypes relative to non-symbiotic ones. Our results provide a rare set of field observations against which predictions from theoretical and experimental work in the evolutionary ecology of RNS can be compared.

A Systematic Literature Review of Healthcare Services on Cloud Services: Application Scenarios, Challenges, and Benefits

The Zero Trust network architecture is an embodiment of the Zero Trust security model, and is progressively being utilized for the improvement of security standards of the current security infrastructures. Fine-grained access control is one of the primary principles of developing zero trust solutions, in which it is expected to manage an overwhelming amount of security policies. Managing the compliance of policies at fine grain level is thus necessary for utmost security stature. This paper aims at developing a novel approach to improve the task of policy management workflow and compliance tracking.

Rising ocean temperatures are threatening marine species and populations worldwide, and ectothermic taxa are particularly vulnerable to warming. Echinoderms are an ecologically important phylum of marine ectotherms and shifts in their population dynamics can have profound impacts on the marine environment. The effects of warming on echinoderms are highly variable across controlled laboratory-based studies. Accordingly, synthesis of these studies will facilitate the better understanding of broad patterns in responses of echinoderms to ocean warming. Herein, a meta-analysis incorporating the results of 85 studies (710 individual responses) is presented, exploring the effects of warming on various performance predictors. The mean responses of echinoderms to all magnitudes of warming were compared across multiple biological responses, ontogenetic life stages, taxonomic classes, and regions, facilitated by multivariate linear mixed effects models. Further models were conducted which only incorporated responses to warming greater than the projected end-of-century mean annual temperatures at the collection sites. This meta-analysis provides evidence that ocean warming will generally accelerate metabolic rate (+ 32%) and reduce survival (– 35%) in echinoderms, and echinoderms from sub-tropical (– 9%) and tropical (– 8%) regions will be the most vulnerable. The relatively high vulnerability of echinoderm larvae to warming (– 20%) indicates that this life stage may be a significant developmental bottleneck in the near-future, likely reducing successful recruitment into populations. Furthermore, asteroids appear to be the class of echinoderms that are most negatively affected by elevated temperature (– 30%). When considering only responses to magnitudes of warming representative of end-of-century climate change projections, the negative impacts on asteroids, tropical species and juveniles were exacerbated (– 51%, – 34%, and – 40% respectively). The results of these analyses enable better predictions of how keystone and invasive echinoderm species may perform in a warmer ocean, and the possible consequences for populations, communities, and ecosystems.

Abstract: Background: Sotrovimab, a monoclonal antibody, is among the approved therapies for coronavirus disease – 2019 (COVID-19). Sotrovimab binds to the spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and inhibits virus attachment to human cells. Real-life experience about the effectiveness of Sotrovimab is limited. We aimed to evaluate the efficacy of Sotrovimab in preventing COVID-19 hospitalizations and other patient-related outcomes as well as the appropriateness of use in an academic hospital in Lebanon. Methodology: In this retrospective observational study, we included adult patients with positive test results for SARS-CoV-2 who received intravenous (IV) Sotrovimab at the American University of Beirut Medical Center (AUBMC) from November 2021 through March 2022. The data collected included patient demographics and comorbidities. Primary outcomes were hospitalization, deterioration after 24 hours, and death due to any cause up to 60 days after the Sotrovimab infusion. Secondary outcomes were progression to critical illness and adverse events. Results: A total of 62 subjects received Sotrovimab infusion at our hospital. More than 50% of the patients had a malignancy. About 77% of the cohort belonged to Tier 1 of the National Institutes of Health (NIH) criteria for Sotrovimab use, and 21% of the patients had clinical deterioration 24 hours after Sotrovimab infusion. The percentage of progression to critical disease was 9.7% and the mortality 6.5 %. Conclusion: Sotrovimab is effective against COVID-19 infection and prevents mortality in high-risk patients.

Routes to diagnosis of Hypopharyngeal cancer: A Single Centre ExperienceINTRODUCTION In the United Kingdom, hypopharyngeal cancer accounts for 3% of head and neck cancers, with an age standardised reported incidence of 0.63 per 10,000. (1). Cancer of the hypopharynx often presents late. Cardinal symptoms of hypopharyngeal cancer include evidence of a neck mass, sore throat, dysphagia, hoarseness and referred otalgia. Referral pathways in patients with suspected head and neck cancer vary (1). They include but are not limited to referral from a primary care setting, acute presentation to secondary care and inter-departmental referral.In 2015, the National Institute for Clinical Excellence (NICE) established guideline NG12; Suspected Cancer, Recognition and Referral Guidelines, which defined the symptoms indicating a possible head and neck (H&N) cancer that warrant further investigation (2). The two symptoms pertinent to timely referral of hypopharyngeal cancer are persistent hoarseness and neck lump. The Northern Cancer Alliance (NCA) has used the NICE guideline to refine its 2 Week Wait (2WW) proforma to be used by healthcare practitioners when cases of H&N cancer are suspected (3). Symptoms that were originally included on the 2WW proforma, and pertinent to hypopharyngeal cancer, included dysphagia, sore throat and referred otalgia. The NCA proforma does not include these symptoms and only includes those recommended by NICE NG12 guidance. At the request of general practitioners (GPs), ‘unexplained, persistent, unilateral enlargement or ulceration of the tonsil or adjacent soft palate’ were included. The proforma does include a free text box encouraging primary care clinicians to describe concerning symptoms that do not fit with the NICE NG12 symptoms. The other symptoms/signs included on the NCA 2WW proforma relate to oral cavity cancer detection. 2WW proformas vary across regional Cancer Alliances in England, with many including dysphagia, sore throat and otalgia. This study aimed to evaluate routes to diagnosis of hypopharyngeal cancer in a large teaching hospital to establish if the current NCA 2WW proforma is appropriate to capture suspected cases of hypopharyngeal cancer.METHODS Basic settings and patient selection This was an observational case review study of all patients with a diagnosis of hypopharyngeal cancer at a large teaching hospital in England between December 2019- July 2022. The audit was registered and approved by the local hospital trust governance department prior to data collection. A total of 68 patients were identified from a prospective H&N audit database. The patient’s NHS number was used to search the hospitals electronic patient record system.Collected data The following parameters were extracted for each case: patient demographics, referral route, time from initial referral to first appointment, Tumour (T), Node (N), Metastases (M) stage, first treatment modality and socio-economic factors; smoking status and index of multiple deprivation decile which was calculated based on the patient’s postcode. A number from one to ten was generated; 1- most deprived lower-layer super output areas (LSOAs) nationally, 10- least deprived 10% of LSOAs nationally. Information regarding referral criteria was recorded from the NCA 2WW proforma. Practitioners could select one or more of the following categories to instigate the 2WW referral pathway:A persistent, unexplained lump in the neck or parotid region of recent onset.Persistent (not intermittent or fluctuating), unexplained hoarseness (over the age of 45 years).Unexplained, persistent, unilateral enlargement or ulceration of the tonsil or adjacent soft palate.AnalysisDescriptive data was collated on a spreadsheet and analysed. Analysis adhered to STROBE guidelines.RESULTS Of the 68 patients, 34 (50%) presented via a 2WW pathway, all from GP referrals. 23 (34%) were referred on non-2WW pathways: eight patients were referred by their GP on a routine basis, eight same site inter-departmental referrals and seven referrals were from another hospital site (no 2WW proforma). Three referrals were identified through routine departmental follow-up (FU) within ENT. Eight patients presented to the ENT service via an emergency route and were not previously known to the service (Figure 1). Characteristics of the patient group are shown in Table 1.Data on the time from initial referral to first appointment date was available for 50 of the 68 patients. 97% (n=33) of patients referred on the 2WW pathway were seen within 14 days of initial referral date. One patient waited 23 days, having rescheduled their appointment. The median time from initial 2WW referral to first appointment date was nine days (range 2-23 days). Of the 50 patients in total, median time from initial referral to first appointment was 10 days (range 2-117 days).18 patients were lacking data detailing initial referral to first appointment. Eight patients presented via an emergency route and were reviewed by ENT services at the time of presentation. Three patients were identified by routine departmental follow-up, and were lacking an initial referral date. Six patients were referred from other hospital sites with a previous diagnosis of hypopharyngeal cancer and one patient referred on a routine basis from GP was lacking referral documentation.Of the 16 patients referred into ENT services on non-2WW pathways, seven patients presented with dysphagia (44%), five patients presented with odynophagia (31%), two patients presented with a sore throat (13%), one patient presented with globus (6%). One patient was referred after incidental findings on previous imaging (6%). Of those 16 patients, median time from initial referral to initial appointment was 14 days (range 6-117 days). Of those presenting with dysphagia specifically, the mean time from referral to initial appointment was 11 days (range 6-14 days).Of the 34 2WW referrals from general practice, 23 patients were referred with a neck lump, 13 patients with persistent hoarseness and two patients with tonsillar ulceration. For all 2WW referrals, practitioners provided additional clinical information in the ‘reason for referral’ box. 44% of patients presenting via the 2WW pathway with a pre-treatment T category of T4. Analysis of pre-treatment category shown in table 2.26 patients (38%) received palliative radiotherapy as their first treatment modality. Of those referred by the 2WW pathway, 13 (38%) received palliative radiotherapy and four (12%) received radical radiotherapy. Analysis of primary treatment modality categorised via referral route is shown in table 3.DISCUSSION The NCA adopted the NICE NG12 symptom to refine their 2WW suspected cancer referral proforma. Our data suggests that choosing to not include those symptoms that may be suggestive of hypopharyngeal cancer; dysphagia, sore throat and otalgia, does not seem to have negatively impacted on the referral of patients with hypopharyngeal cancer. The majority of patients were seen in a timely manner. McKie et al. (8) evaluated referral patterns and diagnostic efficacy of the UK 2WW pathway, and demonstrated 21.4% of H&N cancers were diagnosed via 2WW pathway. The results from our study showed that half of patients diagnosed with hypopharyngeal cancer were referred on the 2WW pathways. Round et al. (9) demonstrated that over the past decade 2WW referrals for all types of suspected cancer have increased significantly.The ‘reason for referral’ box was populated in 100% of cases. This suggests that if the patient’s general practitioner was sufficiently concerned to detail the patients presenting symptoms, they would do so. Pooled data from previous studies of patients referred with suspected H&N cancer presenting with dysphagia indicated that head and neck cancer was diagnosed in only 5.6% of cases (4,7,8,10). In our study, the patients referred from primary care, via a non-2WW pathway, presenting with dysphagia had a median time from referral to first appointment was 11 days. Even in the absence of a 2WW proforma, this implies that referrals in to our centre were likely marked as urgent by the triaging ENT clinician reviewing these, based on the appropriate information provided by the referring practitioner. Together, these suggest that the 2WW proforma and written communication between primary and secondary care is an effective approach.The 2WW system is a balance of promoting earlier diagnosis with the capacity to investigate patients within 14 days (7). Dysphagia, sore throat and otalgia are clearly concerning symptoms when they occur together and are observed in patients who smoke and/or drink alcohol to excess (1). As individual symptoms, they can be vague and common in nature, overlapping with many of the benign persistent throat symptoms that are commonly assessed in ENT clinics. Patients with these symptoms can overload the capacity of the 2WW referral system thereby potentially delaying the system’s ability to assess higher risk symptoms in a more timely manner (7).Early cancer detection correlates with improved survival rates (5). Previous studies suggest that patients presenting via an emergency route are more likely to present with more advanced disease (5,10). Therefore, emergency presentations with advanced disease remains an area of concern to clinicians. This study highlights the link that patients presenting at a late stage, more commonly present via an emergency route, typically go on to have palliative treatment.CONCLUSION This study suggests that removal of non-NICE guidance H&N symptoms from the NCA 2WW proforma, when combined with an appropriate secondary care triaging system, has not negatively impacted on time from initial referral to diagnosis of hypopharyngeal cancer.

Soil fungal community plays an important role in forest ecosystems, and forest secondary succession is a crucial driver of soil fungal community. However, the driving factors of fungal community and function during temperate forest succession and their potential impact on succession processes are poorly understood. In this study, we investigated the dynamics of the soil fungal community in three temperate forest secondary successional stages (shrublands, coniferous forests, and deciduous broadleaf forests) using high-throughput DNA sequencing coupled with functional prediction via the FUNGuild database. We found that fungal community richness, α-diversity, and evenness decreased significantly during the succession process. Soil available phosphorus and nitrate nitrogen decreased significantly after initial succession occurred, and redundancy analysis showed that both were significant predictors of soil fungal community structure. Among functional groups, fungal saprotrophs as well as pathotrophs represented by plant pathogens were significantly enriched in the early-successional stage, while fungal symbiotrophs represented by ectomycorrhiza were significantly increased in the late-successional stage. The abundance of both saprotroph and pathotroph fungal guilds was positively correlated with soil nitrate nitrogen and available phosphorus content. Ectomycorrhizal fungi were negatively correlated with nitrate nitrogen and available phosphorus content and positively correlated with ammonium nitrogen content. These results indicated that the dynamics of fungal community and function reflected the changes in nitrogen and phosphorus availability caused by the secondary succession of temperate forests. The fungal plant pathogen accumulated in the early-successional stage and ectomycorrhizal fungi accumulated in the late-successional stage may have a potential role in promoting forest succession. These findings contribute to a better understanding of the response of soil fungal communities to the secondary forest succession process and highlight the importance of fungal communities during temperate forest succession.

Protected areas are often regarded as pristine land, but in reality, they require rehabilitation and effective management to prevent increased land degradation. Soil management requires soil maps to make informed decisions, which is difficult to create in protected areas due to the large size of land, limited accessibility, little available soil data and limited budgets of such projects. In this paper a hybrid expert knowledge and machine learning digital soil mapping (DSM) method is used to create such maps for Benfontein, a 9900 ha protected area in the semi-arid region of South Africa. The hybrid method uses soil landscape rules to determine virtual soil observations which is added to the training observations used in a machine learning algorithm to create a soil associations map. Soil properties were assigned to each soil class at the 0.1, 0.5 and 0.9 percentile level, to indicate the range of properties at an 80% certainty. The soil maps were interpreted to indicate soil carbon sequestration potential, soil erodibility and off-road driving potential. The soil association map was acceptable as it achieved a kappa value of 0.69. Additionally, it was determined that the site has a large potential for carbon sequestration, the soils are relatively stable against water erosion, and off-road driving should be prohibited on approximately half of the area. The results indicate that the hybrid DSM method is viable to create useful soil maps to inform management decisions in the unique settings of protected areas.

Our aim was to estimate changes in sexual function and semen quality in men recovering from infection since the Omicron pandemic started in China in late 2022. We collected 1540 questionnaires and assessed male function before infection and acute phase after infection by using International Index of Erectile Function-5, Premature Ejaculation Diagnostic Tool, and Arizona Sexual Experience Scale. We also collected the before and after semen analysis results of 247 male patients. During the acute phase after infection, the proportion of erectile dysfunction was significantly higher than before infection, but ejaculatory function was not significantly altered； In addition, semen analysis showed significant difference in semen concentration, semen activity and PR a+b sperm forward movement after infection compared to pre-infection. Omicron can affect erectile function as well as sexual experience in male patients in the acute phase. The risk factors for decreased sexual function due to Omicron included body temperature and anxiety during infection.

Studying small mammals has a paramount significance for ecological, cultural and economic reasons. A survey on the diversity, abundance and habitat association of small mammals in Wenchi highlands, central Ethiopia, was carried out from August 2019 to January 2021. Small mammals were trapped from six different habitats (Hagenia Woodland, Erica Scrub, Qibate, Lakeshore, Erica and Albesa Forests) using Sherman and snap traps in standard trapping grids. A total of 935 rodents belonging to 12 species (Arvicanthis abyssinicus, Desmomys yaldeni, Mastomys natalensis, M. awashensis, Stenocephaylemys albipes, Lophuromys flavopunctatus, L. brevicaudus, L. chrysopus, Dendromus lovati, Lophiomys imhausi, Graphirius murinus, and an unidentified murid rodent), and 24 insectivores belonging to 3 species (Crocidura bailey, C. fumosa and C. olivieri) were recorded. Hystrix cristata and Tachyoryctes splendens were also recorded through indirect evidences. About 52.9% of the identified small mammals were endemic to Ethiopia. A significant variation was observed in the captures of small mammals. The capture rate was higher in live traps (23.85%) than snap traps (8.26%). The diversity and distribution of small mammal species varied among habitats. The highest species diversity (H’=1.74) was recorded in Albesa Forest, while the least was in Qibate Forest (1.43). The highest number of individuals were recorded in Lakeshore Forest (27.73%), whereas the least was in Erica Forest (4.27%). M. natalensis (30.86%) and S. albipes (27.53%) were the two most abundant species, whereas L. imhausi (0.1%) was the least. Wenchi montane forests are one of the most important homes to unique small mammals that need urgent conservation actions.

Background Childhood cancer is the sixth leading cause of global cancer burden. Indeed, 90% of childhood cancer cases occur in low-middle-income countries (LMICs), where mortality can be 4-5 times higher than in high income settings. In addition, many LMICs lack data on pediatric oncology for policy development and resource prioritization. In this paper, we describe the state of pediatric cancer care and treatment in Cameroon. Procedure We conducted cross-sectional survey in July 2020, which enabled us to collect data from two hospitals providing pediatric oncology services in Cameroon. We collected data on service availability, human resource capacity, frequent cancer types, treatment dropout, primary reasons for drop out, disclosure of status, and management of oncology data. Result The surveyed hospitals offered both pediatric chemotherapy and palliative care services; however, none offered nuclear medicine or radiotherapy services. In terms of workforce, human resources were grossly lacking in both hospitals. The available ones include one pediatric hemato-oncologist, one medical oncologist, one resident pediatric oncologist, one pediatric surgeon, and 14 oncology nurses and about 40% (18/45) of have received specialty training in oncology. The commonest childhood cancer managed in these facilities, was Burkitt lymphoma, (39, 23%). About 30% of children on chemotherapy abandoned their treatment, primarily due to lack of funds to continue with treatment sessions. In both settings, the capacity to diagnose cancer and provide counselling was limited. In addition, the tools to capture and transmit data varied by facility, resulting to different data set being generated. Furthermore, both facilities, had no schedule and timelines for data reporting. Conclusions Our results suggest that several factors negatively impact proper cancer care and treatment of pediatric Cancers in Cameroon. These include, inadequate human resource capacity, a high proportion of dropouts from chemotherapy due to high cost, and lack of harmonized data collection and reporting tools and systems. Systematically addressing these factors could contribute to improving treatment outcomes for pediatric cancer patients in Cameroon.

A two degree-of-freedom vibration isolation system with magneto-rheological damper (MRVIS) is analyzed. Under the harmonic excitation, the nonlinear behaviors are discovered. With the excitation frequency increased, the period-doubling bifurcation and saddle node bifurcation, route to chaos are found. Then, the system returns to steady state through the route out of chaos, with inverse period-doubling bifurcation. Furthermore, a sliding mode controller through tracking the error between actual and ideal state system, is proposed to suppress the increasing amplitude of the system caused by the chaos. Both the calculation and experiment show that the chaotic motion is effectively repressed.

This article is a rejoinder to the rebuttal letter authored by Jair Bolsonaro’s former Minister of Health and Secretary of Primary Care to our initial article, “From Bolsonaro to Lula: The opportunity to rebuild universal healthcare in Brazil during the government transition,” published in the International Journal of Health Planning and Management. We aim to refute the claims that we consider unsubstantiated and disconnected from reality, while reiterating the risks posed by authoritarian and antidemocratic far-right governments, such as Bolsonarism in Brazil, to the sustainability and resilience of universal health systems. This political threat is gaining momentum across several countries worldwide, thereby endangering the Democratic Rule of Law, institutions, and social policies. Furthermore, we emphasize the significant actions implemented during the first 100 days of President Lula’s government, which align with the priorities established during the governmental transition process and strengthen the prospects of reconstructing and fortifying the Brazilian universal health system.

The paper describes the detection of exoplanets in multiplanetary systems using HI line data is an approach in astronomy. Traditional methods for detecting exoplanets have limitations in terms of sensitivity and range, which makes it difficult to detect small and distant planets. We propose a mathematical model based on the analysis of the HI line emission and absorption spectra to predict the presence of exoplanets.The model is based on fitting the observed HI line profile to a Gaussian distributionf(v)=Aexp[−(v − vθ)²/(2δv²)] + δf(v) where δf(v) is the perturbation caused by the exoplanet. The amplitude of the perturbation depends on the mass, orbital distance, and other properties of the exoplanet. and searching for significant deviations that may indicate the presence of an exoplanet.The chi-squared statistic,x², measures the difference between the observed and expected HI line profiles: $x^2 =^{\infty} 2^{-n} = 1 [f_{obs}(v) - f_{exp}(v)]^2 / \sigma^2 $. The deviation caused by the exoplanet can be quantified using a perturbation term in the Gaussian distribution. The amplitude of the perturbation depends on the mass, orbital distance, and other properties. We use statistical tests such as the chi-squared test to measure the significance of the deviation and estimate the properties of the exoplanet and the Extragalactic distance scale.

The quantitative identification of nitrate sources is of great significance for the control of non-point source pollution and the comprehensive management of water resources in watersheds. δ 15N-NO 3 - and δ 18O-NO 3 - isotopes combined with the Bayesian isotope mixing model were widely used as effective methods to identify nitrogen sources. In this study, a total of 60 surface water samples and 82 groundwater samples were collected in study area from November 2021 to October 2022, and atmospheric deposition (AD), chemical nitrogen fertilizer (NF), soil nitrogen (SN), and manure and sewage (M&S) were determined as the potential nitrate sources. Source identification by SIAR indicated that in November 2021 the M&S was the main contributor of nitrate to surface water (mean 38.1%), while NF was the main contributor to groundwater (mean 39.8%). In April 2022, NF contributed the most to surface water (38.3%), while groundwater mainly originated from SN (29.4%) and MS (29.8%). The uncertainty analysis showed that the greatest uncertainties were in SN and NF, followed by M&S and AD. Sensitivity analysis showed that the changes in the nitrate isotopic composition of M&S had the greatest effect on the results for δ 15N, whereas only the mean values of oxygen isotope values of AD had a greater effect on the results for δ 18O. The sensitivity analysis results can optimize the sampling scheme and improve the accuracy of the model predictions. Additionally, the contributions of soil nitrogen and nitrogen fertilizer to nitrate in surface water and groundwater reached 58% and 64%, respectively. Therefore, optimizing fertilizer and irrigation management is necessary to improve nitrogen use efficiency in watershed management.

Flame retardants play a crucial role in improving the flame retardant properties of polymer materials. In recent years, environmental problems caused by flame retardants have attracted widespread attention. It is urgent to use green and effective methods to prepare flame retardant polymers. Bioinspired nanocomposites with layered structures seem to provide an effective idea, but in general, the hydrophilic properties of their raw materials limit their applications in certain fields. Here, we prepared biomimetic composites with a layered “brick-and-mortar” structure by gravity-induced deposition using polyimide as the polymer matrix and montmorillonite (MMT) as the filler. The well-arranged structures of the composite material could isolate oxygen and prevent combustible gases from escaping. The gas barrier performance has been greatly improved, in which the water vapor transmission rate (WVTR) and the oxygen transmission rate (OTR) decreased by 99.18% and three orders of magnitude, respectively. The flame retardant performance has also been improved, and its limiting oxygen index can reach 67.9%. More importantly, the polyimide matrix can be converted to water-insoluble by thermal imidization of water-soluble poly (amic acid) salt precursors, which endows the composites with low hygroscopicity. Such coating containing MMT can protect against polyurethane (PU) foam from fire. During the conical calorimetric test, the coated sample self-extinguished, and the peak heat release rate, total heat release, total smoke production is significantly decreased by 53.39%, 40.69%, and 53.03%, respectively. Taking advantage of these properties, this work utilizes a facile method to prepare biomimetic composites with low moisture absorption, excellent gas barrier properties, and flame retardancy, which have great application potential.