bluuebunny/crossref_metadata_2025 huggingface dataset:
Projected Public Health Impact of a Universal Rotavirus Vaccination Program in France
Authors: Oluwaseun Sharomi , Cagnan Lauren , Xausa Ilaria , Nachbar Robert B. , Levy Bachelot Laurie , Chen Yao-Hsuan , Carias Cristina
Published: June 2024

Objective:

In June 2022, French health authorities issued a universal recommendation for routine administration and reimbursement of rotavirus vaccines in infants. Given this recent recommendation by French health authorities, we sought to understand the public health impact of a universal rotavirus vaccination strategy compared with no vaccination.

Materials and Methods:

A deterministic, age-structured, nonlinear dynamic transmission model, accounting for herd immunity, was developed. We considered 3 vaccination coverage scenarios: high (95%), medium (75%) and low (55%). Model parameter values were based on published modeling and epidemiological literature. Model outcomes included rotavirus gastroenteritis (RVGE) cases and healthcare resource utilization due to RVGE (hospitalizations, general practitioner or emergency department visits), as well as the number needed to vaccinate to prevent 1 RVGE case (mild or severe) and 1 RVGE-related hospitalization. Model calibration and analyses were conducted using Mathematica 11.3.

Results:

Over 5 years following implementation, RVGE cases for children under 5 years are estimated to be reduced by 84% under a high vaccination coverage scenario, by 72% under a medium vaccination coverage scenario and by 47% under a low vaccination coverage scenario. Across all scenarios, the number needed to vaccinate to avert 1 RVGE case and hospitalization varied between 1.86–2.04 and 24.15–27.44, respectively.

Conclusions:

Rotavirus vaccination with high vaccination coverage in France is expected to substantially reduce the number of RVGE cases and associated healthcare resource utilization.
Reduced Functioning After Hospitalization for COVID-19 Infection
Authors: Smith James M. , Smith Ellen M.T. , Zafron Michelle L. , Bohannon Richard W. , Miller Kenneth , Thiele Alecia , Zeleznik Hallie , Ohtake Patricia J.
Published: June 2024

Background and Purpose:

COVID-19 infection is associated with persistent physical problems, and approximately 2% of the >100 million people in the United States with COVID-19 infection have required hospitalization. The purpose of this review is to identify problems with activity and participation persisting during the first 6 months after hospitalization for COVID-19.

Methods:

A comprehensive search of 5 bibliographic databases was performed for cohort studies examining activity limitations and participation restrictions assessed within 6 months of hospitalization in adults hospitalized with COVID-19 infection. Two reviewers screened titles, abstracts, and full text to determine eligibility. Study methodological quality was assessed using the SIGN Methodology Checklist 3. Study methods, design, and participant outcomes were extracted. Results were summarized in narrative synthesis, and meta-analysis was conducted for 6-minute walk test.

Results:

Titles (n = 2670) were screened, and 26 acceptable to high-quality studies satisfied all eligibility criteria. Within the first 6 months following hospitalization for COVID-19 people experienced activity limitations and participation restrictions, including 16% reduction in 6-minute walk test distance (compared to age and gender-matched norms) and 59% return to employment rate.

Discussion and Conclusion:

The first 6 months following hospitalization for COVID-19 infection are associated with significant reductions in exercise capacity and return to work. Problems associated with post-intensive care syndrome cannot be ruled out as contributing to these findings. Recognition of these problems is essential and should inform hospital discharge planning and rehabilitation services.
Exploring the influence of the impending death discharge tradition on home death rate in Taiwan
Authors: Lin Ming-Hwai , Chou Yiing-Jenq
Published: June 2024

Background:

As modern societies witness a shift from home deaths to hospital deaths, the compromise practice of impending death discharge (IDD) in response to Chinese traditions and changing times deserves further exploration.

Methods:

Using the Longitudinal Generation Tracking Database 2005, a validated cohort of two million randomly sampled National Health Insurance (NHI) beneficiaries, we conducted a retrospective analysis on the places of death for 123 832 individuals from 2008 to 2017.

Results:

Approximately 47.4% of the residents died in hospitals, 45.6% died in their own homes, and 2.4% died in long-term care facilities. Of those who died at home, 27 809 (49.2%) had undergone an IDD and were classified in the IDD group. Over the past decade, there has been a noticeable trend of decreasing home death rates. This trend is mainly due to the decline in the IDD group, which decreased from 29.6% in 2008 to 16.0% in 2017. The percentage of non-IDD group deaths that occurred at home ranged from 21.4% to 24.7%. The logistic regression analyses of all patients admitted to hospital before death revealed that individuals with IDD tend to be women, middle-aged individuals (aged between 50 and 79 years), married, and those residing outside of the six municipalities. Furthermore, the choice for IDD varied with the cause of death, with conditions like sepsis and malignancy recording higher rates as opposed to pneumonia. Patients who were discharged from hospice care were less likely to choose IDD. No association was found between choosing IDD and receiving hospice home care or emergency room visits in the year before death.

Conclusion:

This study investigates factors associated with IDD, informing healthcare professionals on end-of-life care in Chinese culture. Future qualitative or prospective research can offer deeper insights into family dynamics, patient preferences, and other unmeasured factors influencing IDD utilization.
Short-term outcomes of short- and long-course chemoradiotherapy before total mesorectal excision for locally advanced rectal tumors: A single-center study in Taiwan utilizing propensity score matching
Authors: Chang Chih-Hsien , Chang Shih-Ching , Jiang Jeng-Kai , Wang Huann-Sheng , Lan Yuan-Tzu , Lin Chun-Chi , Lin Hung-Hsin , Huang Sheng-Chieh , Cheng Hou-Hsuan , Yang Yi-Wen , Lin Yu-zu
Published: June 2024

Background:

Locally advanced rectal tumors are typically treated with neoadjuvant chemoradiotherapy. Short-course chemoradiotherapy (SCRT, 2500 cGy in five fractions) is a convenient alternative to concurrent chemoradiotherapy with long-course radiotherapy (CCRT, 4500 cGy in 25 fractions) without sacrificing efficacy. We aimed to compare the short-term outcomes of SCRT and CCRT in patients with mid- and low- rectal tumors who underwent total mesorectal excision using real-world data.

Methods:

We retrospectively reviewed the data of patients with locally advanced rectal cancer who underwent radical resection after neoadjuvant chemoradiotherapy from 2011 to 2022. We analyzed the clinicopathological findings and prognostic factors for disease-free and overall survival in the SCRT and CCRT groups and compared the outcomes using propensity score matching.

Results:

Among the 66 patients in the two groups, no disparities were noted in the demographic features, pathological remission, or downstaging rates. Nonetheless, the SCRT group exhibited superior 3-year disease-free survival (81.8% vs 62.1%, p = 0.011), whereas the overall survival did not differ significantly between the two groups. The initial carcinoembryonic antigen (CEA) levels and neoadjuvant SCRT were associated with the recurrence rates [hazard ratio (HR) = 1.13-4.10; HR = 0.19-0.74], but the harvested lymph node count was not (HR = 0.51-1.97).

Conclusion:

Among patients with locally advanced rectal cancer, SCRT combined with four cycles of FOLFOX was shown to enhance short-term disease-free survival. Factors impacting recurrence include the initial CEA level and SCRT, but not the harvested lymph node count.
Pain, Return to Community Status, and 90-Day Mortality Among Hospitalized Patients With Heart Failure
Authors: Smith Asa B. , Jung Miyeon , O'Donnell Daniel , White Fletcher A. , Pressler Susan J.
Published: June 2024

Background

Pain is common among patients with heart failure but has not been examined with short-term discharge outcomes. The purpose was to examine whether pain at discharge predicts return to community status and 90-day mortality among hospitalized patients with heart failure.

Methods

Data from medical records of 2169 patients hospitalized with heart failure were analyzed in this retrospective cohort study. The independent variable was a diagnosis of pain at discharge. Outcomes were return to community status (yes/no) and 90-day mortality. Logistic regression was used to address aims. Covariates included age, gender, race, vital signs, comorbid symptoms, comorbid conditions, cardiac devices, and length of stay.

Results

The sample had a mean age of 66.53 years, and was 57.4% women and 55.9% Black. Of 2169 patients, 1601 (73.8%) returned to community, and 117 (5.4%) died at or before 90 days. Patients with pain returned to community less frequently (69.6%) compared with patients without pain (75.2%), which was a statistically significant relationship (odds ratio, 0.74; 95% confidence interval, 0.57–0.97; P = .028). Other variables that predicted return to community status included age, comorbid conditions, dyspnea, fatigue, systolic blood pressure, and length of stay. Pain did not predict increased 90-day mortality. Variables that predicted mortality included age, liver disease, and systolic blood pressure.

Conclusion

Patients with pain were less likely to return to community but did not have higher 90-day mortality. Pain in combination with other symptoms and comorbid conditions may play a role in mortality if acute pain versus chronic pain can be stratified in a future study.
Pediatric liver transplant recipients are not just young adults: The importance of a structured health care transition program in adult transplant centers
Authors: Yang Nancy , Vittorio Jennifer , King Lindsay Y.
Published: June 2024

Health care transition (HCT) is a vulnerable period that continues into adulthood, even after the transfer of care. Given the growing population of pediatric liver transplant recipients reaching young adulthood, the need for a standardized and multidisciplinary approach to transition that spans from pediatric to adult care is becoming more imperative. In this article, we review the unique challenges and barriers to successful HCT that adolescent and young adults (AYAs) who have undergone liver transplant face, highlight the gap in transition care in the adult setting, and present the Six Core Elements of Health Care TransitionTM as a framework that can be used by adult providers to incorporate AYAs systematically and collaboratively into adult practice. Multidisciplinary HCT programs should be the standard of care for all AYAs with liver transplant, and while implementation is a necessary first step, ongoing efforts to increase awareness, funding, and research on HCTs into adulthood are needed.
A Set of Acupuncture Needles in the Late Qing Dynasty Collected by George Soulié de Morant
Authors: WANG Han , PANG Yichao , ZENG Ruilin , WU Kai
Published: June 2024

In the early 20th century, French vice-consul George Soulié de Morant encountered acupuncture during his visit to China, and then brought it back to France. After more than 100 years, his collection was transported from Paris, France to Kunming, China, and later recognized as a Chinese national third-class precious cultural heritage. Currently housed in the Museum of Western Studies on Chinese Medicine at Yunnan University of Chinese Medicine, this set of instruments includes one needle holder converted from a fan-shaped holder, ten acupuncture needles, and eleven paper tags handwritten in English with names of diseases and body parts. This article attempts to present the basic information and historical appearance of this set of late Qing dynasty acupuncture instruments by reviewing the collection and related research on acupuncture instruments, consulting acupuncture professionals, measuring the detailed information of the set of instruments, and employing a method of translating and summarizing the content of the attached tags.
Determining the association between systematic lupus erythematosus and the occurrence of primary biliary cirrhosis: a systematic review and meta-analysis
Authors: Polpichai Natchaya , Saowapa Sakditad , Chan Shu-Yen , Wattanachayakul Phuuwadith , Danpanichkul Pojsakorn , Fangsaard Panisara , Trongtorsak Angkawipa
Published: June 2024

Background

Autoimmune diseases often coexist; however, the concomitant occurrence of systemic lupus erythematosus (SLE) and primary biliary cirrhosis (PBC) is rare. Therefore, this study aims to provide a comprehensive summary of evidence regarding the co-occurrence of SLE and PBC.

Methods

PubMed, Web of Science, ScienceDirect, and Google Scholar databases were systematically and comprehensively searched for records published up to February 2024. Full-text articles that aligned with the study’s aim were included, while those published in languages other than English and those designed as case reports, reviews, conference abstracts, or editorials were excluded. Statistical analyses were performed using Comprehensive Meta-Analysis software, and methodological quality was assessed using the Newcastle–Ottawa Scale.

Results

Only 14 studies that met the inclusion criteria with 3944 PBC and 9414 SLE patients were included for review and analysis. Pooled data analysis revealed that approximately 1.1% of SLE patients have concomitant PBC (range: 0.02–7.5%), while around 2.7% of PBC patients concurrently have SLE (range: 1.3–7.5%). Furthermore, qualitative data analysis indicated that the prevalence of PBC in SLE patients presenting with hepatic dysfunction or abnormal liver enzymes ranges from 2 to 7.5%.

Conclusion

Although the concomitant occurrence of SLE and PBC is rare, the small proportion of patients where these diseases coexist warrants close monitoring by clinicians. This underscores the importance of surveillance to prevent their co-occurrence.
Effects of Cardiopulmonary Rehabilitation on Cardiorespiratory Fitness and Clinical Symptom Burden in Long COVID
Authors: Besnier Florent , Malo Jacques , Mohammadi Hânieh , Clavet Sarah , Klai Chiheb , Martin Nicolas , Bérubé Béatrice , Lecchino Catia , Iglesies-Grau Josep , Vincent Thomas , Gagnon Christine , Gaudreau-Majeau Flavie , Juneau Martin , Simard François , L’Allier Philippe , Nigam Anil , Gayda Mathieu , Bherer Louis
Published: June 2024

Objective

The aim of the study is to investigate the effectiveness of an 8-wk cardiopulmonary rehabilitation program on cardiorespiratory fitness (VO2peak) and key cardiopulmonary exercise test measures, quality of life, and symptom burden in individuals with long COVID.

Design

Forty individuals with long COVID (mean age 53 ± 11 yrs), were randomized into two groups: (1) rehabilitation group: center-based individualized clinical rehabilitation program (8 wks, 3 sessions per week of aerobic and resistance exercises, and daily inspiratory muscle training) and (2) control group: individuals maintained their daily habits during an 8-wk period.

Results

There was a significant difference between groups in mean VO2peak improvement (P = 0.003). VO2peak improved significantly in the rehab group (+2.7 mL.kg.min; 95% CI = +1.6 to +3.8; P < 0.001) compared to the control group (+0.3 mL.kg.min; 95% CI = −0.8 to +1.3 P = 0.596), along with VE/VCO2 slope (P = 0.032) (−2.4; 95% CI = −4.8 to +0.01; P = 0.049 and +1.3; 95% CI = −1.0 to +3.6; P = 0.272, respectively) and VO2 at first ventilatory threshold (P = 0.045). Furthermore, all symptom impact scales improved significantly in the rehabilitation group compared to the control group (P < 0.05).

Conclusions

An individualized and supervised cardiopulmonary rehabilitation program was effective in improving cardiorespiratory fitness, ventilatory efficiency, and symptom burden in individuals with long COVID. Careful monitoring of symptoms is important to appropriately tailor and adjust rehabilitation sessions.
Impact of a Sensor-Based Platform on the Outcome of Medial Off-Loader Bracing in Individuals With Knee Osteoarthritis
Authors: Darcy Rose , Couri Juliana , Newkirk Keira , Neagu Remus , Darbhe Vikram , Jayabalan Prakash
Published: June 2024

Objective

The aim of the study is to determine the effectiveness of a medial off-loader brace with sensor monitoring capabilities and associated phone application in improving outcomes for individuals with knee osteoarthritis.

Methods

This is a randomized clinical trial of participants with knee osteoarthritis, aged 40–75 with two groups: 1) brace-only and 2) brace+sensor (sensor providing walking time, knee range of motion, and 7-day activity streak). Both groups received a prefabricated custom-fitted medial off-loader brace and 12-wk self-guided exercise therapy program. Baseline and postintervention assessments included subjective and objective outcomes.

Results

Sixty participants were recruited (n = 30/group). The brace+sensor group demonstrated higher study retention (88.89%) compared with the brace-only group (73.33%). Significant improvement in Knee Injury and Osteoarthritis Outcome Survey knee pain and other Knee Injury and Osteoarthritis Outcome Survey subscores compared with baseline was observed for both groups. However, only the brace+sensor group improved beyond the established minimal clinically important difference for Knee Injury and Osteoarthritis Outcome Survey pain (11.31 ± 13.87). Knee Injury and Osteoarthritis Outcome Survey activities of daily living was also significantly improved in the brace+sensor group compared with brace-only group (P = 0.049). Both treatment groups had significant improvement in functional outcomes (10-m walk, 5× sit-to-stand, P < 0.05). Only the brace+sensor group had significant improvements in the 6-min walk test (P = 0.02) and reduction in participant weight (P = 0.01) at 12 wks.

Conclusions

Incorporating wearable technology in standard bracing for individuals with knee osteoarthritis has potential in improving clinical outcomes.
Ultrasound-Guided Supraorbital Nerve Block as a Diagnostic Tool in the Outpatient Physiatry Setting
Authors: Myers Keith , Stitik Todd , Liu Shiyu , Tollin Noah
Published: June 2024

Here, we describe a case in which an ultrasound-guided supraorbital nerve block was used for the purposes of confirming the diagnosis of trigeminal neuralgia associated with herpes zoster and determining which trigeminal nerve branch is the pain generator in a patient with clinically suggestive findings. We discuss how performing a nerve block at the site of where the affected nerve exits the skull may identify which nerve is mediating the patient’s symptoms and therefore guide possible further treatment options, which could potentially provide a more lasting duration of relief.
LYMPHOSCORE (Lymphoscintigraphy Scoring Reliability) Reliability of a New Qualitative and Semiquantitative Lymphoscintigraphy Scoring System for Primary Lymphedema
Authors: Guillemard Sophie , Moulis Lionel , Ilonca Diana , Mestre Sandrine , Deshayes Emmanuel , Quéré Isabelle , Adham Salma
Published: June 2024

Purpose of the Report

Primary lymphedema (PLE) is a rare chronic disorder. Extremity lymphoscintigraphy offers access for dynamic and functional information on peripheral lymphatics and lymph nodes. We aimed to assess intraobserver and interobserver reliability of a new lymphoscintigraphy quantitative and qualitative scoring system in a homogeneous population of adult patients followed for PLE of the lower limb(s).

Patients and Methods

This is a monocentric retrospective study. Clinical files of patients who underwent a lymphoscintigraphy were reviewed for inclusion. Lymphoscintigraphies were interpreted twice by 2 observers with a washout period. To assess intraobserver and interobserver reliability for both lower limbs, Cohen κ and Gwet’s AC1 reliability coefficients were calculated with 95% confidence interval and P value of the zero-reliability comparison test. To interpret reliability coefficients, we used the orders of magnitude reported by Landis and Koch.

Results

One hundred forty-four patients (288 limbs) with PLE were included. For intraobserver reliability, agreement range was 0.87–1 with an almost perfect agreement in all staging items of the score for both limbs with the lower limit of the 95% confidence interval ≥80%. Interobserver reliability was overall strong or almost perfect, ranging from 0.67 to 0.97.

Conclusions

This new scoring system demonstrated excellent intraobserver reliability and a very good interobserver reliability. Lymphoscintigraphy, when performed in a referral center and interpreted by trained nuclear medicine physicians, is a reliable means of investigation in patients with PLE of the lower limbs. This reproducibility advocates for further use of lymphoscintigraphy in multicentric cohorts of PLE patients.
A Dwindling Matter
Authors: Saxton Anthony T. , Monreal Alberto J. , Stang Michael T. , Kazaure Hadiza S. , Scheri Randall P.
Published: June 2024

Objective:

To evaluate Medicare reimbursement trends for endocrine surgeries from 2000-23.

Background:

As the population ages, demand for endocrine surgeries is expected to increase. Understanding reimbursement trends is essential to ensure the financial sustainability of endocrine surgery.

Methods:

Data were extracted from Medicare Inpatient and Outpatient Hospital datasets, National Summary, and Physician Fee Look-up Files for nine common thyroid, parathyroid and adrenal surgeries. Data were adjusted for inflation. Descriptive statistics, compound annual growth rate (CAGR), and linear regression models were built to evaluate practice and reimbursement trends.

Results:

From 2000-23, there was a 63.8% increase in endocrine surgery volume. However, inflation-adjusted average procedure reimbursements decreased by 43.2% from $1709 to $972 (CAGR -2.4%), which is the largest decrease for any surgical subspecialty reported in the published literature. At the current CAGR, the average estimated reimbursement is projected to decrease to $868 by 2030 (P<0.001). Average facility reimbursements for inpatient and outpatient hospitalizations increased. However, substantial practice pattern shifts in the study period led to decreased overall facility reimbursements, with a $17.9 million decrease in total inpatient reimbursements between 2016-21 that was only partially offset by a $3.2 million increase in outpatient hospital reimbursements.

Conclusion:

Medicare procedure reimbursements for endocrine surgeries have been outpaced by inflation, with large decreases since 2000. Concurrent changes in practice patterns have also resulted in markedly fewer inpatient stays leading to lower total facility reimbursements. Our data raise concern over the financial sustainability of the endocrine surgery field as the demand for endocrine surgery procedures increases.
Does Hyperventilation Increase the Diagnostic Yield of the Routine Electroencephalogram: A Retrospective Analysis of Adult and Pediatric Cohorts
Authors: Nadarajah Neerrajah , Fahey Michael , Seneviratne Udaya
Published: June 2024

Purpose:

While hyperventilation (HV) increases the diagnostic yield of EEG in children, there is conflicting evidence to support its application in adults. For the first time in history, a large cohort of patients has undergone EEGs without HV during the COVID-19 pandemic. Utilizing this opportunity, we sought to investigate whether HV increases the diagnostic yield of EEG in children compared with adults.

Methods:

Patients aged six years and above who had routine EEGs at Monash Health between January 2019 and December 2020 were studied. The cohort was divided into two, pediatric (younger than 18 years) and adult (18 years or older). Epileptiform abnormalities (ictal and interictal) were the outcomes investigated. The effect of HV was examined with logistic regression to determine odds ratios with 95% confidence intervals.

Results:

In total, we studied 3,273 patients (pediatric = 830, adult = 2,443). In the pediatric cohort, HV significantly increased the diagnostic yield of absence seizures (p = 0.01, odds ratios 2.44, 95% confidence intervals 1.21–4.93). In adults, HV did not increase the yield of absence seizures (p = 0.34, odds ratios 0.36, 95% confidence intervals 0.05–2.88). Interictal epileptiform discharges during HV were significantly more frequent in children compared with adults (p < 0.001, odds ratios 3.81, 95% confidence intervals 2.51–5.77).

Conclusions:

Hyperventilation is useful to increase the yield of interictal epileptiform discharges and absence seizures in pediatric patients but not in adults. Hence, routine EEG may be recorded in adults without HV when it is unsafe to perform.
Demographic effects of aggregation in the presence of a component Allee effect
Authors: Jorge Daniel C. P. , Martinez-Garcia Ricardo
Published: June 2024

The component Allee effect (AE) is the positive correlation between an organism’s fitness component and population density. Depending on the population spatial structure, which determines the interactions between organisms, a component AE might lead to positive density dependence in the population per-capita growth rate and establish a demographic AE. However, existing spatial models impose a fixed population spatial structure, which limits the understanding of how a component AE and spatial dynamics jointly determine the existence of demographic AEs. We introduce a spatially explicit theoretical framework where spatial structure and population dynamics are emergent properties of the individual-level demographic and movement rates. This framework predicts various spatial patterns depending on its specific parametrization, including evenly spaced aggregates of organisms, which determine the demographic-level by-products of the component AE. We find that aggregation increases population abundance and allows population survival in harsher environments and at lower global population densities when compared with uniformly distributed organisms. Moreover, aggregation can prevent the component AE from manifesting at the population level or restrict it to the level of each independent aggregate. These results provide a mechanistic understanding of how component AEs might operate for different spatial structures and manifest at larger scales.
Investigating the impact of temperature on growth rate of the root rot fungus, Gymnopus fusipes
Authors: Pettifor Bethany J. , Kajamuhan Anparasy , Denman Sandra , McDonald James E.
Published: June 2024

Gymnopus fusipes is an understudied root rot pathogen associated with multiple tree species and is linked to episodes of oak decline across the United Kingdom and Europe. Although the reported distribution of G. fusipes is broad, many observations rely solely on visual identification of fruiting bodies, which can be unreliable, and lack confirmation by molecular and/or isolation data to verify this broad ecological range. Given the paucity of information regarding the true ecological distribution of G. fusipes, it is difficult to predict and model the potential distribution of the species under both current and future climate scenarios. In this study, to determine the growth capabilities of G. fusipes across a range of ecologically relevant temperatures, five geographically diverse isolates of G. fusipes were grown at five different temperatures ranging from 4–37°C, to determine the optimal temperature for G. fusipes growth, and to establish whether geographically diverse isolates exhibit local adaptation to temperature tolerance. Incubation temperature had a significant effect on G. fusipes growth rate, with 25°C representing the optimum (P<0.001). Isolates had differing growth rates at each of the temperatures, with an isolate from the UK having the highest overall growth rate across all five temperatures tested (P<0.001), and at the optimum, increased by a mean value of over 4915 mm2. Local adaptation to temperature tolerance was not found in the isolates tested. These data demonstrate the optimal incubation temperature for future laboratory studies on G. fusipes and provide the first data on the growth rate of this pathogen across ecologically relevant climate ranges that may inform land managers, modellers, and policy makers in predicting the current and potentially future geographical limits of this widespread root rot pathogen.
Identification of key genes and signaling pathway in the pathogenesis of Huntington's disease via bioinformatics and next generation sequencing data analysis
Authors: Vastrad Basavaraj Mallikarjunayya , Vastrad Chanabasayya Mallikarjunayya
Published: June 2024

Huntington's disease (HD) is the primary cause of progressive motor deficits, psychiatric symptoms, and cognitive impairment. The exact molecular mechanisms of HD pathogenesis are largely unknown. This investigation aims to identify the hub genes, miRNA and TFs in HD and explore their potential molecular regulatory network. Next generation sequencing (NGS) dataset (GSE105041) was extracted from the Gene Expression Omnibus (GEO) database. An integrated bioinformatics pipeline including identification of differentially expressed genes (DEGs), Gene ontology and REACTOME pathway enrichment analysis, protein-protein interaction (PPI) network and module analysis, miRNA-hub gene regulatory network analysis and TF-hub gene regulatory network analysis, and receiver operating characteristic curve (ROC) analysis were applied to identify hub genes, miRNA and TFs, and key drivers of HD pathogenesis. We identified 958 DEGs in the discovery phase, consisting of 479 up regulated genes and 479 down regulated genes. GO and REACTOME enrichment analyses of the 479 up regulated genes and 479 down regulated genes showed that they were mainly involved in multicellular organismal process, developmental process, signaling by GPCR and MHC class II antigen presentation. Further analysis of the PPI network using Cytoscape and PEWCC plugins identified 10 hub genes, including LRRK2, MTUS2, HOXA1, IL7R, ERBB3, EGFR, TEX101, WDR76, NEDD4L and COMT. Possible target miRNAs and TFs, including hsa-mir-1292-5p, hsa-mir-4521, ESRRB and SREBF1, were predicted by constructing a miRNA-hub gene regulatory network analysis and TF-hub gene regulatory network. This investigation used bioinformatics methods to explore the molecular pathogenesis of HD, and identified potential molecular markers. These molecular markers might provide novel ideas and methods for the early diagnosis, treatment, and monitoring of HD.
Candida glabratamaintains two Hap1 homologs, Zcf27 and Zcf4, for distinct roles in ergosterol gene regulation to mediate sterol homeostasis under azole and hypoxic conditions
Authors: Saha Debasmita , Gregor Justin B. , Hoda Smriti , Eastman Katharine E. , Navarrete Mindy , Wisecaver Jennifer H. , Briggs Scott D.
Published: June 2024

Candida glabrataexhibits innate resistance to azole antifungal drugs but also has the propensity to rapidly develop clinical drug resistance. Azole drugs, which target Erg11, is one of the three major classes of antifungals used to treatCandidainfections. Despite their widespread use, the mechanism controlling azole-inducedERGgene expression and drug resistance inC. glabratahas primarily revolved around Upc2 and/or Pdr1. In this study, we determined the function of two zinc cluster transcription factors, Zcf27 and Zcf4, as direct but distinct regulators ofERGgenes. Our phylogenetic analysis revealedC. glabrataZcf27 and Zcf4 as the closest homologs toSaccharomyces cerevisiaeHap1. Hap1 is a known zinc cluster transcription factor inS. cerevisiaein controllingERGgene expression under aerobic and hypoxic conditions. Interestingly, when we deletedHAP1orZCF27in eitherS. cerevisiaeorC. glabrata,respectively, both deletion strains showed altered susceptibility to azole drugs, whereas the strain deleted forZCF4did not exhibit azole susceptibility. We also determined that the increased azole susceptibility in azcf27Δstrain is attributed to decreased azole-induced expression ofERGgenes, resulting in decreased levels of total ergosterol. Surprisingly, Zcf4 protein expression is barely detected under aerobic conditions but is specifically induced under hypoxic conditions. However, under hypoxic conditions, Zcf4 but not Zcf27 was directly required for the repression ofERGgenes. This study provides the first demonstration that Zcf27 and Zcf4 have evolved to serve distinct roles allowingC. glabratato adapt to specific host and environmental conditions.

IMPORTANCE

Invasive and drug-resistant fungal infections pose a significant public health concern.Candida glabrata, a human fungal pathogen, is often difficult to treat due to its intrinsic resistance to azole antifungal drugs and its capacity to develop clinical drug resistance. Therefore, understanding the pathways that facilitate fungal growth and environmental adaptation may lead to novel drug targets and/or more efficacious antifungal therapies. While the mechanisms of azole resistance inCandidaspecies have been extensively studied, the roles of zinc cluster transcription factors, such as Zcf27 and Zcf4, inC. glabratahave remained largely unexplored until now. Our research shows that these factors play distinct yet crucial roles in regulating ergosterol homeostasis under azole drug treatment and oxygen-limiting growth conditions. These findings offer new insights into how this pathogen adapts to different environmental conditions and enhances our understanding of factors that alter drug susceptibility and/or resistance.
ERK3/MAPK6 promotes triple-negative breast cancer progression through collective migration and EMT plasticity
Authors: Morazzo Sofia , Fernandes Soraia , Fortea Marina , Skálová Helena , Cassani Marco , Vrzalová Kamila , Kafka Filip , Vrbský Jan , Pereira de Sousa Daniel , Bosáková Veronika , Shin Jaeyoung , Fric Jan , Haase Kristina , Forte Giancarlo
Published: June 2024

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and is associated with high cell plasticity, recurrence, and metastatic rate. During epithelial-to-mesenchymal transition (EMT), cancer cells display EMT plasticity, or partial-EMT features, which are required for breast cancer metastasis, such as collective migration. ERK3 has been implicated in promoting migration and invasion of breast cancer, but the mechanisms remain elusive. Here, we investigated ERK3 expression across patient-derived datasets of breast cancer and established its association with aggressive breast cancer phenotypes and poor clinical outcomes. Leveraging the hypothesis that ERK3 contributes to TNBC progression by supporting a partial-EMT state, we showed that ERK3 is essential in different steps of the metastatic process, especially by enabling collective migration but also by modulating cell-extracellular matrix adhesion, anchorage-independent growth, extravasation and colonization. In conclusion, our results demonstrate that ERK3 contributes to TNBC progression and potentially metastasis by promoting EMT plasticity and collective migration.
Knockdown of DJ-1 Resulted in a Coordinated Activation of the Innate Immune Antiviral Response in HEK293 Cell Line
Authors: Zohar Keren , Linial Michal
Published: June 2024

PARK7, also known as DJ-1, plays a critical role in protecting cells by functioning as a sensitive oxidation sensor and modulator of antioxidants. DJ-1 acts to maintain mitochondrial function and regulate transcription in response to different stressors. In this study, we show that cell lines vary by their antioxidation potential at basal condition. The transcriptome of HEK293 cells was tested following knockdown (KD) of DJ-1 using siRNAs which reduced the DJ-1 transcripts to only 12% of the original level. We compared the expression levels of 14k protein coding transcripts, and 4.2k non-coding RNAs relative to control cells treated with non-specific siRNAs. Among the coding genes, ∼200 upregulated differentially expressed genes (DEGs) signified a coordinated antiviral innate immune response. Most genes were associated with regulation of type 1 interferons (IFN) and induction of inflammatory cytokines. About a quarter of these genes were also induced in cells treated by non-specific siRNAs that were used as a negative control. Beyond the antiviral response, 114 genes were specific to KD of DJ-1 with enrichment in RNA metabolism and mitochondrial functions. A smaller set of downregulated genes (58 genes) were associated with dysregulation in membrane structure, cell viability, and mitophagy. We propose that KD of DJ-1 diminish its protective potency against oxidative stress, rendering the cells labile and responsive to dsRNA signal by activation of a large number of genes, many of which drive apoptosis, cell death, and inflammatory signatures. The KD of DJ-1 highlights its crucial role in regulating genes associated with antiviral responses, RNA metabolism, and mitochondrial functions, apparently through alteration in STAT activity and downstream signaling. Given that DJ-1 is highly expressed in metastatic cancers, targeting DJ-1 could be a promising therapeutic strategy where manipulation of DJ-1 level may reduce cancer cell viability and enhance the efficacy of cancer treatments.
Targeting MDSC-HTR2B to Improve Immune Checkpoint Inhibitors in Breast to Brain Metastasis
Authors: Iyer Mukund , Das Diganta , Baugh Aaron G. , Shah Priya , Nakamura Brooke , Sedighi Saman , Reed Max , Jang Julie , Chow Frances , Torres Evanthia Roussos , Neman Josh
Published: June 2024

Myeloid Derived Suppressor Cells (MDSCs) support breast cancer growth via immune suppression and non-immunological mechanisms. Although 15% of patients with breast cancer will develop brain metastasis, there is scant understanding of MDSCs’ contribution within the breast-to-brain metastatic microenvironment. Utilizing co-culture models mimicking a tumor-neuron-immune microenvironment and patient tissue arrays, we identified serotonergic receptor, HTR2B, on MDSCs to upregulate pNF-κB and suppress T cell proliferation, resulting in enhanced tumor growth.In vivomurine models of metastatic and intracranial breast tumors treated with FDA-approved, anti-psychotic HTR2B antagonist, clozapine, combined with immunotherapy anti-PD-1 demonstrated a significant increase in survival and increased T cell infiltration. Collectively, these findings reveal a previously unknown role of MDSC-HTR2B in breast-to-brain metastasis, suggesting a novel and immediate therapeutic approach using neurological drugs to treat patients with metastatic breast cancer.
Impact of Climate, Habitat and Scale on the Population Dynamics of Feral Goats on the Isle of Rùm, NW Scotland
Authors: Dunbar R.I.M.
Published: June 2024

Although feral goats are an invasive species renowned for their ability to survive in degraded habitats, their capacity to occupy high latitude habitats is severely restricted. I analyse long term data on the lifehistory and demography of a feral goat population on the Isle of Rùm, NW Scotland, in relation to both longterm variation in climatic variables and within-population variation in environmental variables. While exhibiting many features characteristic of ungulate lifehistory, goats are especially sensitive to variations in thermal conditions, especially during winter. This is compounded by the fact that, at the latitude of Rùm, goats give birth in mid-winter, even though this imposes significant stress on both mother and kid. Longterm patterns in population growth rates are correlated with winter temperature and the NAO index, with little evidence for density-dependent effects (except in respect of fertility). In addition, there was evidence that the presence of a large sympatric red deer population was limiting the goats’ capacity to increase by denying them access to preferred foraging habitat. Nonetheless, their unusual sensitivity to the thermal environment implies that the goat population will increase significantly with progressive climate warming.
Onset of α5GABA-A Receptor Dependent Hippocampal Trisynaptic Circuit Dysfunction Is Associated Increased Age and Blood Pressure
Authors: Ratner Marcia H. , Wainford Richard , Farb David H.
Published: June 2024

Hypertension onset with aging is of widespread clinical significance, predominantly in males, yet the neural circuitry underpinnings for hypertension associated memory dysfunction remains unknown. Sprague Dawley (SD) male but not female rats develop age dependent increases in mean arterial blood pressure (MAP) by 16 months of age. We sought to interrogate the functional integrity of the hippocampal trisynaptic circuit (HTC), which is known to participate in memory, to determine whether age-associated increases in MAP contributes to circuitry dysfunction that may lead to mild-cognitive impairment (MCR). Ripples, and specifically sharp-wave ripple oscillations, play a role in memory replay and consolidation during awake immobility among other behaviors. These synchronous high frequency local field potentials (LFPs) in the ripple band (140 to 200 Hz) serve as an HTC level surrogate marker for circuitry function in rodents, non-human primates, and humans. Thus, we asked whether age-associated increased MAP might alter ripple dynamics. Recognizing that each patient responds in a unique way to hypertension we used a within subject design wherein each animal served as its own control in the investigative model. We surgically implanted high density silicon probe electrodes in HTC CA1 of young and aged SD males to determine whether a nootropic drug, α5IA, a negative allosteric modulator of α5 subunit containing type-A GABA receptors, could detect aberrant modulation of ripples within each subject. Here we report that acute oral administration of α5IA selectively modulated ripple amplitude, but not its duration or frequency during epochs of awake immobility. The response of peak ripple amplitude to α5IA is substantially diminished when chronic MAP exceeds 160 mmHg, corresponding to significant hypertension. The results are consistent with a model in which age-associated increases in MAP is associated with dysfunctional α5 GABA-A receptor modulation of ripple amplitude, but not duration or frequency, as a potential precision biomarker for memory dysfunction.

Age-related neurogenic hypertension disrupts memory and ripple band neural circuitry function in the hippocampal trisynaptic circuit involved in memory consolidation.
The physiology of deterrence: Flicker vertigo and its application in avian management
Authors: Honda Takeshi
Published: June 2024

Human-bird conflicts are in a critical state, involving economic losses such as agricultural losses, bird strikes on aircraft and avian influenza. Traditional technologies leveraging bird vision and hearing often lose their effectiveness over time as birds become habituated to these stimuli. To address these challenges, our study introduces a novel countermeasure technology based on neurophysiology. The human brain reacts to flickering light, which can cause symptoms like headaches, nausea, and dizziness. In extremely rare cases, it can even lead to epilepsy. This led us to consider the possibility that similar stimuli could be applicable to birds. In our experiments conducted during the day, we used long-range flashlights. White flickering light had no effect on bird escape behavior. However, when cellophane film was attached to the flashlights to restrict the wavelength, the emitted red light induced escape behavior in birds. Additionally, employing two types of flashlights to generate flickering red+blue or red+green lights elicited escape behavior. However, the blue and green combination proved to be less effective. These results are highly similar to those found in human neurophysiology, showing that red light alone and the combination of red and blue lights have the most significant impact on the brain. By measuring the flight initiation distance (FID) of birds, we found that illuminated areas had a significantly higher FID (137m) compared to non-illuminated areas (12m). These findings suggest that applying principles of human physiology to wildlife management can offer new solutions for bird damage control.
Alzheimer’s disease as a form of in situ diabetes: A systematic review and meta-analysis of therapeutic approaches using intranasal insulin treatment
Authors: de Oliveira Andrade Luís Jesuíno , Matos de Oliveira Gabriela Correia , Matos de Oliveira Luís
Published: June 2024

Introduction

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is characterized by the loss of memory, language, and other cognitive functions. Increasing evidence suggests that AD shares pathophysiological similarities with type 2 diabetes, leading to the concept of AD as “diabetes in situ” within the brain. Intranasal insulin (INI) for AD has emerged as a promising therapeutic approach due to its ability to directly target the brain and modulate insulin signaling pathways.

Objective

To evaluate the efficacy and safety of INI therapy for AD through a systematic review and meta-analysis of randomized clinical trials.

Method

A comprehensive search across electronic databases, including PubMed, Web of Science, Scopus, and Embase, was conducted to identify relevant studies published up to June 2024. Studies were included if they met the following criteria: original research articles published in peer-reviewed journals; focused on humans; investigated the therapeutic effects of INI administration on cognitive impairment associated with AD or diabetes; reported quantitative data on cognitive outcomes, biomarkers, or pathological markers relevant to AD or diabetes. For studies with available data, a meta-analysis was conducted to quantitatively synthesize the effects of INI on cognitive outcomes. METAANALYSISONLINE (https://metaanalysisonline.com/), an online statistical tool, was employed to conduct the meta-analysis and generate forest plots and funnel plots.

Results

A total of 647 articles were identified through electronic database searches using predefined search terms, and eight studies met the inclusion criteria and were selected for data extraction and analysis. Based on the analysis performed using random effects model with Mantel-Haenszel method to compare the odds ratio, the overall odds ratio was 3.75 with a 95% confidence interval of 1.49 - 9.4. The test for overall effect shows a significance at p<0.05. The The I2value indicates that 85.5% of the variability among studies arises from heterogeneity rather than random chance.

Conclusion

While the data is not yet definitive enough to establish INI as a definitive treatment for AD, the accumulating evidence supporting its safety, efficacy, and reduced systemic side effects strongly suggests that INI is associated with an overall enhancement of global cognition.