bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of SARS-CoV-2 Infection on the Association Between Laboratory Tests and Severe Outcomes Among Hospitalized Children
Authors: Xie Jianling , Kuppermann Nathan , Florin Todd A , Tancredi Daniel J , Funk Anna L , Kim Kelly , Salvadori Marina I , Yock-Corrales Adriana , Shah Nipam P , Breslin Kristen A , Chaudhari Pradip P , Bergmann Kelly R , Ahmad Fahd A , Nebhrajani Jasmine R , Mintegi Santiago , Gangoiti Iker , Plint Amy C , Avva Usha R , Gardiner Michael A , Malley Richard , Finkelstein Yaron , Dalziel Stuart R , Bhatt Maala , Kannikeswaran Nirupama , Caperell Kerry , Campos Carmen , Sabhaney Vikram J , Chong Shu-Ling , Lunoe Maren M , Rogers Alexander J , Becker Sarah M , Borland Meredith L , Sartori Laura F , Pavlicich Viviana , Rino Pedro B , Morrison Andrea K , Neuman Mark I , Poonai Naveen , Simon Norma-Jean E , Kam April J , Kwok Maria Y , Morris Claudia R , Palumbo Laura , Ambroggio Lilliam , Navanandan Nidhya , Eckerle Michelle , Klassen Terry P , Payne Daniel C , Cherry Jonathan C , Waseem Muhammad , Dixon Andrew C , Ferre Isabel Beneyto , Freedman Stephen B
Published: October 2023

Background

To assist clinicians with identifying children at risk of severe outcomes, we assessed the association between laboratory findings and severe outcomes among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–infected children and determined if SARS-CoV-2 test result status modified the associations.

Methods

We conducted a cross-sectional analysis of participants tested for SARS-CoV-2 infection in 41 pediatric emergency departments in 10 countries. Participants were hospitalized, had laboratory testing performed, and completed 14-day follow-up. The primary objective was to assess the associations between laboratory findings and severe outcomes. The secondary objective was to determine if the SARS-CoV-2 test result modified the associations.

Results

We included 1817 participants; 522 (28.7%) SARS-CoV-2 test-positive and 1295 (71.3%) test-negative. Seventy-five (14.4%) test-positive and 174 (13.4%) test-negative children experienced severe outcomes. In regression analysis, we found that among SARS-CoV-2-positive children, procalcitonin ≥0.5 ng/mL (adjusted odds ratio [aOR], 9.14; 95% CI, 2.90–28.80), ferritin >500 ng/mL (aOR, 7.95; 95% CI, 1.89–33.44), D-dimer ≥1500 ng/mL (aOR, 4.57; 95% CI, 1.12–18.68), serum glucose ≥120 mg/dL (aOR, 2.01; 95% CI, 1.06–3.81), lymphocyte count <1.0 × 109/L (aOR, 3.21; 95% CI, 1.34–7.69), and platelet count <150 × 109/L (aOR, 2.82; 95% CI, 1.31–6.07) were associated with severe outcomes. Evaluation of the interaction term revealed that a positive SARS-CoV-2 result increased the associations with severe outcomes for elevated procalcitonin, C-reactive protein (CRP), D-dimer, and for reduced lymphocyte and platelet counts.

Conclusions

Specific laboratory parameters are associated with severe outcomes in SARS-CoV-2-infected children, and elevated serum procalcitonin, CRP, and D-dimer and low absolute lymphocyte and platelet counts were more strongly associated with severe outcomes in children testing positive compared with those testing negative.
Dengue Encephalopathy or Dengue Encephalitis? You Decide
Authors: Durkin Simon M , da Silva Andrea L , Davies Nicholas W S , Sriskandan Shiranee
Published: October 2023

Awareness of neurological sequelae of dengue fever is increasing. However, as this case illustrates, there is a diagnostic conundrum in determining whether certain features are in keeping with dengue encephalopathy or dengue encephalitis. Further consensus is required.
The Perils of Overly Sensitive Viral Load Testing for Persons With Human Immunodeficiency Virus
Authors: Rodriguez Maria G , Syros Alina , Rodriguez Allan E , Serota David P
Published: October 2023

The concept of “undetectable = untransmittable (U = U)” has been revolutionary in both the prevention and treatment of persons with human immunodeficiency virus (HIV). Most studies proving the concept of U = U used an HIV RNA (viral load [VL]) cutoff of 200 copies/mL to define being undetectable. Since then, increasingly sensitive commercial VL assays, sometimes down to a lower limit of detection (LLD) of 20 copies/mL, lead to confusion about the definition of “undetectable” and when someone is truly considered untransmittable. VLs between the LLD and 200 copies/mL have been associated with future virologic failure; however, no data exist to suggest that intervening in those patients leads to any meaningful benefits. In the absence of a demonstrable benefit of reporting such low VLs, we view this practice as harmful. We suggest recommendations for adjusting VL reporting and improving provider counseling, and call for research designs to mitigate the harms of overly sensitive VL testing.
The Influence of Undercooling and Sector Zoning on Clinopyroxene–Melt Equilibrium and Thermobarometry
Authors: MacDonald Alice , Ubide Teresa , Mollo Silvio , Pontesilli Alessio , Masotta Matteo
Published: October 2023

Thermobarometry provides a critical means of assessing locations of magma storage and dynamics in the lead-up to volcanic eruptions and crustal growth. A common approach is to utilise minerals that have compositions sensitive to changes in pressure and/or temperature, such as clinopyroxene, which is ubiquitous in mafic to intermediate magmas. However, clinopyroxene thermobarometry may carry significant uncertainty and require an appropriate equilibrium melt composition. In addition, the degree of magma undercooling (ΔT) affects clinopyroxene composition and zoning, with common sector zoning potentially obfuscating thermobarometry results. Here, we use a set of crystallisation experiments on a primitive trachybasalt from Mt. Etna (Italy) at ΔT = 25–233 °C, P = 400–800 MPa, H2O = 0–4 wt % and fO2 = NNO + 2, with clinopyroxene crystals defined by Al-rich zones (prisms and skeletons) and Al-poor zones (hourglass and overgrowths) to assess common equilibrium models and thermobarometric approaches. Under the studied conditions, our data suggest that the commonly applied Fe–Mg exchange (cpx-meltKdFe–Mg) is insensitive to increasing ΔT and may not be a reliable indicator of equilibrium. The combined use of DiHd (CaMgSi2O6 + CaFeSi2O6) and EnFs (Mg2Si2O6 + Fe2Si2O6) models indicate the attainment of equilibrium in both Al-rich and Al-poor zones for almost all investigated ΔT. In contrast, CaTs (CaAl2SiO6) and CaTi (CaTiAl2O6) models reveal substantial deviations from equilibrium with increasing ΔT, particularly in Al-rich zones. We postulate that this reflects slower diffusion of Al and Ti in the melt compared with Ca and Mg and recommend the concurrent application of these four models to evaluate equilibrium between clinopyroxene and melt, particularly for sector-zoned crystals.

Thermobarometers calibrated with only isothermal–isobaric experiments closely reproduce experimental P–T at low ΔT, equivalent to natural phenocrysts cores and sector-zoned mantles. Models that also consider decompression experiments are most accurate at high ΔT and are therefore suitable for outermost phenocryst rims and groundmass microlites. Recent machine learning approaches reproduce P–T conditions across all ΔT conditions. Applying our experimental constraints to sector-zoned microphenocrysts and groundmass microlites erupted during the 1974 eccentric eruption at Mt. Etna, we highlight that both hourglass and prism sectors are suitable for thermobarometry, given that equilibrium is sufficiently tested for. The combination of DiHd, EnFs, CaTs and CaTi models identifies compositions closest to equilibrium with the bulk melt composition, and results in smaller differences in P–T calculated for hourglass and prism sectors compared with applying only DiHd and EnFs equilibrium models. This provides a framework to assess crystallisation conditions recorded by sector-zoned clinopyroxene crystals in mafic alkaline settings.
Inhibition of TLR4 signalling to dampen joint inflammation in osteoarthritis
Authors: Bartels Yvonne L , van Lent Peter L E M , van der Kraan Peter M , Blom Arjen B , Bonger Kimberly M , van den Bosch Martijn H J
Published: October 2023

Local and systemic low-grade inflammation, mainly involving the innate immune system, plays an important role in the development of OA. A receptor playing a key role in initiation of this inflammation is the pattern-recognition receptor Toll-like receptor 4 (TLR4). In the joint, various ligands for TLR4, many of which are damage-associated molecular patterns (DAMPs), are present that can activate TLR4 signalling. This leads to the production of pro-inflammatory and catabolic mediators that cause joint damage. In this narrative review, we will first discuss the involvement of TLR4 ligands and signalling in OA. Furthermore, we will provide an overview of methods for inhibit, TLR4 signalling by RNA interference, neutralizing anti-TLR4 antibodies, small molecules and inhibitors targeting the TLR4 co-receptor MD2. Finally, we will focus on possible applications and challenges of these strategies in the dampening of inflammation in OA.
Adolescent Cybervictimization in 31 Countries: The Gender Gap, Gendered Opportunity, and the Contextual Influence of Gender Stratification
Authors: Deryol Rustu , McNealey Rachel L , Wilcox Pamela
Published: October 2023

This study examined the gender gap, gendered opportunity, and the contextual influence of gender inequality and women’s absolute status with respect to online stalking victimization and online image-based victimization (IBV) among youths in 31 countries. Descriptive analysis allowed for comparison of prevalence of online stalking and IBV across gender. We estimated sex-specific hierarchical logistic regression models that examined the relationships between indicators of risky lifestyle, social attachments, physical/social vulnerability and online stalking victimization and IBV. We estimated multilevel models that focused on the linear and curvilinear effects of country-level gender inequality and women’s absolute status (WAS) on the average country-level odds of online stalking victimization and IBV. There were both cross-gender similarities and differences regarding the individual-level correlates of both types of adolescent cybervictimization examined. Countries that had relatively greater gender inequality tended to exhibit a higher prevalence of boys’ and girls’ victimization. Findings suggest that student-level programs should address risk, vulnerability, and protective factors across the three student life domains of risky lifestyle, social attachments, and physical and social vulnerability. Addressing risky lifestyle seems particularly important for reducing girls’ victimization. Moreover, reducing gender inequality or increasing women’s absolute status can play a role in reducing youth online victimization generally.
Heart Rot Disease of Walnut Caused by Nothophoma juglandis sp. nov. and Its Endophytic Biocontrol Agent
Authors: Zhao Lili , Sun Wei , Zhang Lin , Yin Yueqi , Xie Yuqing , Zhang Ying
Published: October 2023

English walnut (Juglans regia L.) is an economically important hardwood tree species cultivated worldwide. Walnut heart rot disease leading to heartwood decay of trees has been frequently observed in a number of plantations in China. To identify the causal agent, 29 diseased stem samples were collected from walnut plantations in Beijing, and 54 fungal isolates were obtained. Koch’s postulates were developed, and the results showed that Nothophoma juglandis, a species new to science, was the causal agent of walnut heart rot disease. Granulobasidium vellereum, a notable biocontrol agent, was coisolated with N. juglandis. An antagonistic assay on dual culture and walnut stems (both in the field and detached branches) proved that G. vellereum acted as a potential biocontrol agent against N. juglandis, as it could significantly inhibit the expansion of N. juglandis. The optimal temperature for mycelial growth and pathogenicity of N. juglandis was 26.6 and 27.0°C, respectively, which frequently occur in the summer of the walnut-growing regions in China.
Evaluation of the Everyday Memory Questionnaire-Revised in a menopausal population: understanding the brain fog during menopause
Authors: Zhu Chen , Thomas Elizabeth HX , Li Qi , Arunogiri Shalini , Thomas Natalie , Gurvich Caroline
Published: October 2023

Objective

Brain fog (ie, memory complaints and concentration difficulties) is frequently reported during the menopausal transition. There is lack of standardized scales available to measure brain fog across the menopausal transition. This study aimed to evaluate the factor structure of the Everyday Memory Questionnaire-Revised (EMQ-R) and to determine the most commonly reported everyday cognitive symptoms in a menopausal population.

Methods

Four hundred seventeen eligible women aged from 40 to 60 years (107 premenopausal, 149 perimenopausal, and 161 early postmenopausal) were recruited from the general community and were included in the analyses. Confirmatory factor analysis was conducted to test the model fit of the bifactor structure (ie, 4-item attentional subscale ranged 0-16, 7-item retrieval subscale ranged 0-28) of the 13-item EMQ-R (ranged 0-52) in a menopausal populations. Typical items in the retrieval subscale include “difficulty finding words,” the attentional subscale include “difficulty following the thread of a story,” and analysis of variance and multivariate analysis of covariance were used to investigate the group differences of individual items and two subscales.

Results

Confirmatory factor analysis indicated the bifactor structure of the EMQ-R has a good fit in all three groups. A significant difference was identified in the mean retrieval scores (pre: 11.8, peri: 13.6, early post: 11.7) but not in the mean attentional scores (pre: 4.53, peri: 5.01, early post: 4.65).

Conclusions

The EMQ-R retrieval subscale may serve as a potential instrument to assess memory retrieval symptoms that contribute to “brain fog” in menopause. Increased memory retrieval complaints reported by the perimenopausal group suggests a transition-related memory retrieval dysfunction during menopausal transition.
Clinical Ultrasound Training in Emergency Medicine Advanced Practice Provider Residencies
Authors: Junker Christian , Vakkalanka Priyanka , Wittrock Cory
Published: October 2023

Introduction

Clinical ultrasound training is essential to any emergency medicine (EM) clinician's skill set. We aim to understand the current training patterns of clinical ultrasound training within Advanced Practice Provider (APP) residencies.

Methods

In a survey sent electronically to 17 active EM APP residencies, data were obtained from 21 responses to questions about structure of ultrasound faculty, quality assessment, feedback, and competency evaluation.

Results

We had a response rate of 88%. Of programs surveyed, 93% were associated with EM physician residencies with 87% led by an ultrasound fellowship-trained EM physician. Ninety-three percent of programs required proctored scanning. Sixty percent of programs do not have any required number of scans to graduate.

Conclusion

We found that most EM APP residencies share clinical ultrasound faculty, structures, and processes with associated EM physician residencies. We believe that quality training within clinical ultrasound is attainable; however, proficiency guidelines across EM APP residency programs are lacking.
Long-Term Medical Treatment and Adherence in Patients With Left Ventricular Assist Devices: A Danish Nationwide Cohort Study
Authors: Schjødt Inge , Mols Rikke E. , Eiskjær Hans , Bakos István , Horváth-Puhó Erzsébet , Gustafsson Finn , Kristensen Søren L. , Larsson Johan E. , Løgstrup Brian B.
Published: October 2023

The use of a left ventricular assist device (LVAD) in treating advanced heart failure has increased. However, data regarding medical treatment and adherence following LVAD implantation is sparse, particularly whether socioeconomic factors (cohabitation status, educational level, employment status, and income) and multimorbidity influence these aspects, which are known to impact adherence in heart failure patients. We performed a nationwide cohort study of 119 patients with LVAD implanted between January 1, 2006, and December 31, 2018, who were discharged alive with LVAD therapy. We linked individual-level data from clinical LVAD databases, the Scandiatransplant Database, and Danish medical and administrative registers. Medical treatment 90-day pre-LVAD and 720-day post-LVAD were assessed using descriptive statistics in 90-day intervals. Medication adherence (proportion of days covered ≥80%) was assessed 181- to 720-day post-LVAD. The proportions of patients using angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (88.7%), beta-blockers (67.0%), mineralocorticoid receptor antagonists (62.9%), warfarin (87.6%), and aspirin (55.7%) within 90-day post-LVAD were higher than pre-LVAD and were stable during follow-up. Medication adherence ranged from 86.7% (aspirin) to 97.8% (warfarin). Socioeconomic factors and multimorbidity did not influence medical medication use and adherence. Among LVAD patients, medical treatment and adherence are at high levels, regardless of socioeconomic background and multimorbidity.
Using a Low-Flow Extracorporeal Carbon Dioxide Removal (ECCO2R) System in the Management of Refractory Status Asthmaticus: A Case Series
Authors: Fox Steven , Mehkri Omar , Latifi Mani , Krishnan Sudhir , Dill Tracey , Duggal Abhijit
Published: October 2023

Rescue treatments for status asthmaticus remain limited. Current literature has mainly focused on using extracorporeal membrane oxygenation (ECMO) as a primary modality of care for these patients. Low-flow extracorporeal CO2 removal (ECCO2R) systems are an attractive option to improve refractory hypercapnic respiratory acidosis because of status asthmaticus. This is a retrospective case series that describes the feasibility and efficacy of the use of a low-flow ECCO2R device, the Hemolung Respiratory Assist System, in patients with refractory hypercapnic respiratory failure because of status asthmaticus. Eight patients were treated with the Hemolung Respiratory Assist System in eight separate locations globally. Seven (88%) of the patients survived to discharge in this case series. Both CO2 and pH resolution were seen in 6 hours. None of the ECCO2R runs were stopped because of mechanical- or device-related complications. One patient necessitated transition to ECMO. Low-flow ECCO2R systems is an effective option for resolution of refractory hypercapnia in status asthmaticus. Use of these systems are also associated with a survival rate of close to 90% in patients with status asthmaticus.
Impact of emergency department length of stay on in-hospital mortality: a retrospective cohort study
Authors: Balen Frederic , Routoulp Simon , Charpentier Sandrine , Azema Olivier , Houze-Cerfon Charles-Henri , Dubucs Xavier , Lauque Dominique
Published: October 2023

Background and importance

Emergency Department (ED) workload may lead to ED crowding and increased ED length of stay (LOS). ED crowding has been shown to be associated with adverse events and increasing mortality. We hypothesised that ED-LOS is associated with mortality.

Objective

To study the relationship between ED-LOS and in-hospital mortality.

Design

Observational retrospective cohort study.

Settings and participants

From 1 January 2015 to 30 September 2018, all visits by patients aged 15 or older to one of the two ED at Toulouse University Hospital were screened. Patients admitted to the hospital after ED visits were included. Visits followed by ED discharge, in-ED death or transfer to ICU or another hospital were not included.

Outcome measure and analysis

The primary outcome was 30-day in-hospital mortality. ED-LOS was defined as time from ED registration to inpatient admission. ED-LOS was categorised according to quartiles [<303 min (Q1), between 303 and 433 minutes (Q2), between 434 and 612 minutes (Q3) and >612 min (Q4)]. A multivariable logistic regression tested the association between ED-LOS and in-hospital mortality.

Main results

A total of 49 913 patients were admitted to our hospital after ED visits and included in the study. ED-LOS was not independently associated with in-hospital mortality. Compared to ED-LOS < 303 min (Q1, reference), odd-ratios (OR) [95% CI] of in-hospital mortality for Q2, Q3, and Q4 were respectively 0.872 [0.747–1.017], 0.906 [0.777–1.056], and 1.137 [0.985–1.312]. Factors associated to in-hospital mortality were: aged over 75 years (OR [95% CI] = 4.3 [3.8–4.9]), Charlson Comorbidity Index score > 1 (OR [95% CI] = 1.3 [1.1–1.5], and 2.2 [1.9–2.5] for scores 2 and ≥ 3 respectively), high acuity at triage (OR [95% CI] = 3.9 [3.5–4.4]), ED visit at Hospital 1 (OR [95% CI] = 1.6 [1.4–1.7]), and illness diagnosis compared to trauma (OR [95% CI] = 2.1 [1.7–2.6]). Night-time arrival was associated with decreased in-hospital mortality (OR [95% CI] = 0.852 [0.767–0.947]).

Conclusion

In this retrospective cohort study, there was no independent association between ED-LOS before admission to general non-ICU wards and in-patient mortality.
Association between mortality and phone-line waiting time for non-urgent medical care: a Danish registry-based cohort study
Authors: Mills Elisabeth Helen Anna , Møller Amalie Lykkemark , Gnesin Filip , Zylyftari Nertila , Jensen Britta , Christensen Helle Collatz , Blomberg Stig Nikolaj , Kragholm Kristian Hay , Gislason Gunnar , Køber Lars , Gerds Thomas , Folke Fredrik , Lippert Freddy , Torp-Pedersen Christian , Andersen Mikkel Porsborg
Published: October 2023

Background and importance

Telephone calls are often patients’ first healthcare service contact, outcomes associated with waiting times are unknown.

Objectives

Examine the association between waiting time to answer for a medical helpline and 1- and 30-day mortality.

Design, setting and participants

Registry-based cohort study using phone calls data (January 2014 to December 2018) to the Capital Region of Denmark’s medical helpline. The service refers to hospital assessment/treatment, dispatches ambulances, or suggests self-care guidance.

Exposure

Waiting time was grouped into the following time intervals in accordance with political service targets for waiting time in the Capital Region: <30 s, 0:30–2:59, 3–9:59, and ≥10 min.

Outcome measures and analysis

The association between time intervals and 1- and 30-day mortality per call was calculated using logistic regression with strata defined by age and sex.

Main results

In total, 1 244 252 callers were included, phoning 3 956 243 times, and 78% of calls waited <10 min. Among callers, 30-day mortality was 1% (16 560 deaths). For calls by females aged 85–110 30-day mortality increased with longer waiting time, particularly within the first minute: 9.6% for waiting time <30 s, 10.8% between 30 s and 1 minute and 9.1% between 1 and 2 minutes. For calls by males aged 85–110 30-day mortality was 11.1%, 12.9% and 11.1%, respectively. Additionally, among calls with a Charlson score of 2 or higher, longer waiting times were likewise associated with increased mortality. For calls by females aged 85–110 30-day mortality was 11.6% for waiting time <30 s, 12.9% between 30 s and 1 minute and 11.2% between 1 and 2 minutes. For calls by males aged 85–110 30-day mortality was 12.7%, 14.1% and 12.6%, respectively. Fewer ambulances were dispatched with longer waiting times (4%/2%) with waiting times <30 s and >10 min.

Conclusion

Longer waiting times for telephone contact to a medical helpline were associated with increased 1- and 30-day mortality within the first minute, especially among elderly or more comorbid callers.
High-density lipoprotein functionality, cardiovascular health, and patterns of alcohol consumption: new insights and future perspectives
Authors: Trius-Soler Marta , Mukamal Kenneth J. , Guasch-Ferré Marta
Published: October 2023

Purpose of review

Cardiovascular diseases (CVD) pose a significant public health challenge, contributing to 422 million disability-adjusted life years in 2021. The role of high-density lipoproteins (HDL) and alcohol consumption, one of their major modifiable determinants, remains controversial. The objective of this review is to provide a comprehensive narrative overview of HDL functionality and its predictive value for CVD in relation to patterns of alcohol consumption.

Recent findings

HDL phenotypes beyond HDL-cholesterol (HDL-c) such as distribution of HDL subspecies, HDL particle abundance, and reverse cholesterol transport capacity are promising indicators of atherosclerotic CVD risk. Low-to-moderate alcohol consumption seems to improve HDL functionality and reduce the incidence of CVD among primarily middle-aged men and postmenopausal women. Advancements in our understanding of HDL biogenesis, structure, and function hold promise for improving HDL-related measures and their predictive value for cardiovascular health.

Low-to-moderate alcohol consumption appears to not only increase HDL-c concentration found in the HDL fraction of plasma but also enhance HDL functionality, providing insights into the underlying mechanisms linking alcohol exposure and cardiovascular health benefits. However, rigorous, well designed intervention trials of alcohol consumption on hard cardiovascular outcomes are needed to identify robust causal associations of HDL phenotypes and alcohol consumption with cardiovascular risk.
The Experiences of Female Partners of Patients With Erectile Dysfunction Due to Prostate Cancer Treatment in China
Authors: Wang Tong , Cheng Hui-Lin , Li Kai-Wen , Wong Ping Kit Kitty , Dong Wen
Published: October 2023

Background

Because of sociocultural factors, Chinese female partners of patients with prostate cancer (PC) may have perspectives and needs that differ from the more published reports of female partners living in Western cultures.

Objectives

The aim of this study was to explore the experiences of female partners of patients with PC experiencing erectile dysfunction in China.

Interventions/Methods

In this interpretive descriptive design, qualitative data were collected from semistructured telephone interviews with purposively sampled participants from the urology outpatient unit in a hospital in South China. The interviews were audiotaped, transcribed, and analyzed using a constant comparison approach.

Results

Three themes emerged from the analysis of the participants’ narratives: (a) acceptance of ceasing sex; (b) preserving intimacy through caregiving; and (c) the need for sexual health–related information.

Conclusion

Participants in this study reported that their own sexuality and intimacy were affected by their partner’s erectile dysfunction, but they adjusted to sexuality and intimacy changes through their caregiving of their husbands owing to Chinese traditional perspectives on women’s obligations. They also reported having unmet informational needs in improving sexual well-being for the sake of their partners, lending further support to the likely benefit of couple-based educational interventions addressing sexual wellness in dyads affected by PC and erectile dysfunction.

Implications for Practice

The present study findings highlighted the need for more research attention to the support of Chinese female partners of patients with PC regarding sexual and intimate topics.
CAMHS Clinician Attitudes to Borderline Personality Disorder in Adolescence Across Scotland
Authors: Foubister Louise , Simpson Struan
Published: October 2023

Child and Adolescent Mental Health Service (CAMHS) clinicians have been reported to hold negative views toward the diagnosis of borderline personality disorder (BPD) in adolescence. We aimed to reevaluate with the expectation that recent advances have nurtured more positive attitudes. One hundred ninety clinicians working across CAMHS in Scotland completed a 16-item electronic survey of attitudes to BPD, derived from the Attitudes and Skills Questionnaire. Eighty-three percent of psychiatrists, 72% of nurses, and 37% of psychologists surveyed agreed that BPD is a valid diagnosis in adolescence, and 92%, 74%, and 44%, respectively, were willing to make this diagnosis. CAMHS clinicians were more optimistic compared with clinicians working in adult mental health services. CAMHS clinicians' responses may indicate increased acceptance of BPD in the adolescent population. There is a thirst for workforce education and training. Consideration should be taken to actively move the focus of identification and diagnosis of BPD into CAMHS rather than the current culture of late diagnosis.
Introducing the Staff-Administered Meal Independence Rating Scale for Use Among Patients With Serious Mental Illnesses
Authors: Ehntholt Amy , Fu En , Pope Leah G. , Rotter Merrill , Compton Michael T.
Published: October 2023

For individuals living with serious mental illnesses (SMIs), inadequate meal preparation skills can hinder the ability to live independently; yet rating scales tailored for this population are lacking. We describe development, item analysis, and initial reliability and validity of the Staff-Administered Meal Independence Rating Scale (SAMIRS). After item development involving expert consultation, two rounds of pilot testing (n = 188, n = 293) were conducted in inpatient and residential settings (transitional living residences [TLRs] and community residences [CRs]). For initial testing of convergent validity, Pearson correlations with Specific Levels of Functioning (SLOF) scale items were computed. Exploratory factor analysis revealed a single factor; Cronbach's alpha was high (0.98). The mean SAMIRS score varied by setting: CR residents scored higher than those in TLRs or inpatient units. Scores were highly correlated with SLOF items measuring community living skills. Although further study is warranted, the SAMIRS could be a useful tool in rating functional needs pertaining to meal independence among individuals with SMI.
Outcomes of Early versus Standard Closure of Diverting Ileostomy after Proctectomy
Authors: Emile Sameh Hany , Horesh Nir , Garoufalia Zoe , Gefen Rachel , Ray-Offor Emeka , Wexner Steven D.
Published: October 2023

Objective:

We aimed to compare outcomes of early and standard closure of diverting loop ileostomy (DLI) after proctectomy and determine risk factors for anastomotic leak (AL) and complications.

Summary Background Data:

Formation of DLI has been a routine practice after proctectomy to decrease the incidence and potential adverse sequela of AL.

Methods:

PubMed, Scopus and Web of Science were searched for randomized controlled trials (RCTs) that compared outcomes of early versus standard closure of DLI after proctectomy. Main outcome measures were postoperative complications, AL, ileus, surgical site infection (SSI), reoperation, readmission, and hospital stay following DLI closure.

Results:

Eleven RCTs (932 patients; 57% male) were included. Early closure group included 474 patients and standard closure 458 patients. Early closure was associated with higher odds of AL (OR: 2.315, P=0.013) and similar odds of complications (OR: 1.103, P=0.667), ileus (OR: 1.307, P=0.438), SSI (OR:1.668, P=0.079), reoperation (OR: 1.896, P=0.062) and readmission (OR: 3.431, P=0.206). Hospital stay was similar (WMD: 1.054, P=0.237). Early closure had higher odds of AL than standard closure when early closure was done ≤2 weeks (OR: 2.12, P=0.047) but not within 3-4 weeks (OR: 2.98, P=0.107). Factors significantly associated with complications after early closure were diabetes mellitus, smoking, and closure of DLI ≤2 weeks whereas factors associated with AL were ≥ASA II classification and diabetes mellitus.

Conclusions:

Early closure of DLI after proctectomy has a higher risk of AL, particularly within two weeks of DLI formation. On the basis of this study, routine early ileostomy closure cannot be recommended.
Pan-genome of pear provides insights into the fruit quality traits differentiation between Asian and European pears
Authors: Ding Baopeng , Hu Haifei , Liu Tingting , Qamar Muhammad Tahir ul , Lin Yujing , Xu Ruirui , Chen Zhiwen , Song Yuqin , He Guangqi , Han Youzhi , Guo Huangping , Qiao Jun , Zhao Jianguo , Feng Xinxin , Yang Sheng , He Shaofang , Li Liulin , Varshney Rajeev K. , Guo Xuhu
Published: October 2023

The pear (Pyrus spp.) is a remarkable fruit, well known for its diverse flavors, textures, culinary versatility, and global horticultural importance. However, the genetic diversity responsible for its extensive phenotypic variations remains largely unexplored. Here, wede novoassembled and annotated the genomes of the maternal (PsbM) and paternal (PsbF) lines of the hybrid ‘Yuluxiang’ pear and constructed the first pear pangenome of 1.15Gb by combining these two genomes with five previously published pear genomes. Using the constructed pangenome, we identified 21,224 gene PAVs and 1,158,812 SNPs in the non-reference genome that were absent in the PsbM reference genome. Compared with SNP markers, we found that PAV-based analysis provides additional insights into the pear population structure. In addition, we also revealed that some genes associated with pear fruit quality traits have differential occurrence frequencies and differential gene expression between Asian and European populations. Moreover, our analysis of the pear pangenome revealed a mutated SNP and an insertion in the promoter region of the genePsbMGH3.1potentially enhances sepal shedding in ‘Xuehuali’ which is vital for pear quality. This research helps further capture the genetic diversity of pear populations and provides valuable genomic resources for accelerating pear breeding.
Pathogenic Morphological Signatures of Perturbations in Mitochondrial-Related Genes Revealed by Pooled Imaging Assay
Authors: Kremitzki Colin , Waligorski Jason , Bachman Graham , Mohammed Ali Lina , Bramley John , Vakaki Maria , Chandrasekaren Vinay , Patel Purva , Mather Dhruv , Hime Paul , Mitra Robi , Milbrandt Jeff , Buchser William
Published: October 2023

Mutations in mitochondrial-related genes underlie numerous neurodegenerative diseases, yet the significance of most variants remains uncertain concerning disease phenotypes. Several thousand genes have been shown to regulate mitochondria in eukaryotic cells, but which of these genes are necessary for proper mitochondrial dynamics? We investigated the degree of morphological disruptions in mitochondrial gene-silenced cells to understand the magnitude of genetic contribution to properly functioning mitochondria and to identify pathogenic variants. We analyzed 5,835 gRNAs in a high dimensional phenotypic dataset produced by the image-based pooled analysis platform Raft-Seq. Using the MFN2-mutant cell phenotype, we identified several genes, including TMEM11, TIMM8A, and three NADH Ubiquinone proteins, as crucial for normal mitochondrial morphology in human U2OS cells. Additionally, we found several missense and UTR variants within the genes SLC25A19 and ATAD3A as drivers of mitochondrial aggregation. By examining multiple features instead of a single readout, this analysis was powered to detect genes which had morphological ‘signatures’ aligned with MFN2-mutant phenotypes. Reanalysis with anomaly detection revealed other critical genes, including APOOL, MCEE, NIT, PHB, and SLC16A7, which perturb mitochondrial network morphology in a manner divergent from MFN2. These studies offer insights into the molecular basis for mitochondrial dysfunction, setting the stage for new genomic diagnostics and therapeutic discovery.
Cellular rejuvenation protects neurons from inflammation mediated cell death
Authors: Drake Sienna S. , Mohammadnia Abdulshakour , Heale Kali , Groh Adam M.R. , Hua Elizabeth M.-L. , Zaman Aliyah , Hintermayer Matthew A. , Zandee Stephanie , Gosselin David , Stratton Jo Anne , Sinclair David A. , Fournier Alyson E.
Published: October 2023

In multiple sclerosis (MS), the invasion of the central nervous system by peripheral immune cells is followed by the activation of resident microglia and astrocytes. This cascade of events results in demyelination, which triggers neuronal damage and death. The molecular signals in neurons responsible for this damage are not yet fully characterized. In MS, retinal ganglion cell neurons (RGCs) of the central nervous system (CNS) undergo axonal injury and cell death. This phenomenon is mirrored in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. To understand the molecular landscape, we isolated RGCs from mice subjected to the EAE protocol. RNA-sequencing and ATAC-sequencing analyses were performed. Pathway analysis of the RNA-sequencing data revealed that RGCs displayed a molecular signature, similar to aged neurons, showcasing features of senescence. Single-nucleus RNA-sequencing analysis of neurons from human MS patients revealed a comparable senescence-like phenotype., which was supported by immunostaining RGCs in EAE mice. These changes include alterations to the nuclear envelope, modifications in chromatin marks, and accumulation of DNA damage. Transduction of RGCs with anOct4-Sox2-Klf4transgene to convert neurons in the EAE model to a more youthful epigenetic and transcriptomic state enhanced the survival of RGCs. Collectively, this research uncovers a previously unidentified senescent-like phenotype in neurons under pathological inflammation and neurons from MS patients. The rejuvenation of this aged transcriptome improved visual acuity and neuronal survival in the EAE model supporting the idea that age rejuvenation therapies and senotherapeutic agents could offer a direct means of neuroprotection in autoimmune disorders.
Antagonists of the stress and opioid systems restore the functional connectivity of the prefrontal cortex during alcohol withdrawal through divergent mechanisms
Authors: Carrette L.L.G. , Santos A. , Brennan M. , Othman D. , Collazo A. , George O.
Published: October 2023

Chronic alcohol consumption leads to dependence and withdrawal symptoms upon cessation, contributing to persistent use. However, the brain network mechanisms by which the brain orchestrates alcohol withdrawal and how these networks are affected by pharmacological treatments remain elusive. Recent work revealed that alcohol withdrawal produces a widespread increase in coordinated brain activity and a decrease in modularity of the whole-brain functional network using single-cell whole-brain imaging of immediate early genes. This decreased modularity and functional hyperconnectivity are hypothesized to be novel biomarkers of alcohol withdrawal in alcohol dependence, which could potentially be used to evaluate the efficacy of new medications for alcohol use disorder. However, there is no evidence that current FDA-approved medications or experimental treatments known to reduce alcohol drinking in animal models can normalize the changes in whole-brain functional connectivity. In this report, we tested the effect of R121919, a CRF1 antagonist, and naltrexone, an FDA-approved treatment for alcohol use disorder, on whole-brain functional connectivity using the cellular marker FOS combined with graph theory and advanced network analyses. Results show that both R121919 and naltrexone restored the functional connectivity of the prefrontal cortex during alcohol withdrawal, but through divergent mechanisms. Specifically, R121919 increased FOS activation in the prefrontal cortex, partially restored modularity, and normalized connectivity, particularly in CRF1-rich regions, including the prefrontal, pallidum, and extended amygdala circuits. On the other hand, naltrexone decreased FOS activation throughout the brain, decreased modularity, and increased connectivity overall except for the Mu opioid receptor-rich regions, including the thalamus. These results identify the brain networks underlying the pharmacological effects of R121919 and naltrexone and demonstrate that these drugs restored different aspects of functional connectivity of the prefrontal cortex, pallidum, amygdala, and thalamus during alcohol withdrawal. Notably, these effects were particularly prominent in CRF1-and Mu opioid receptors-rich regions highlighting the potential of whole-brain functional connectivity using FOS as a tool for identifying neuronal network mechanisms underlying the pharmacological effects of existing and new medications for alcohol use disorder.
Growth Dynamics of Ductal Carcinoma in Situ Recapitulate Normal Breast Development
Authors: Ryser Marc D. , Greenwald Matthew A. , Sorribes Inmaculada C. , King Lorraine M. , Hall Allison , Geradts Joseph , Weaver Donald L. , Mallo Diego , Holloway Shannon , Monyak Daniel , Gumbert Graham , Vaez-Ghaemi Shariar , Wu Ethan , Murgas Kevin , Grimm Lars J. , Maley Carlo C. , Marks Jeffrey R. , Shibata Darryl , Hwang E. Shelley
Published: October 2023

Ductal carcinoma in situ (DCIS) and invasive breast cancer share many morphologic, proteomic, and genomic alterations. Yet in contrast to invasive cancer, many DCIS tumors do not progress and may remain indolent over decades. To better understand the heterogenous nature of this disease, we reconstructed the growth dynamics of 18 DCIS tumors based on the geo-spatial distribution of their somatic mutations. The somatic mutation topographies revealed that DCIS is multiclonal and consists of spatially discontinuous subclonal lesions. Here we show that this pattern of spread is consistent with a new ‘Comet’ model of DCIS tumorigenesis, whereby multiple subclones arise early and nucleate the buds of the growing tumor. The discontinuous, multiclonal growth of the Comet model is analogous to the branching morphogenesis of normal breast development that governs the rapid expansion of the mammary epithelium during puberty. The branching morphogenesis-like dynamics of the proposed Comet model diverges from the canonical model of clonal evolution, and better explains observed genomic spatial data. Importantly, the Comet model allows for the clinically relevant scenario of extensive DCIS spread, without being subjected to the selective pressures of subclone competition that promote the emergence of increasingly invasive phenotypes. As such, the normal cell movement inferred during DCIS growth provides a new explanation for the limited risk of progression in DCIS and adds biologic rationale for ongoing clinical efforts to reduce DCIS overtreatment.
A Cross-sectional Feasibility Study to Evaluate the Usability and Efficacy of “Swaasa”: An AI-Platform for Rapid Respiratory Health Assessment
Authors: Lotheti Siva Kumar , Vissamsetti Haritha , Pamarthi kiran , Bhimarasetty Devi Madhavi , Rudraraju Gowrisree , Rao Sripada Narayana , Gottipulla Charishma , Firmal Priyanka , Mamidgi Baswaraj , Palreddy Shubha Deepti , Bhoge Nikhil kumar Reddy , Narreddy Harsha Vardhan Reddy , Yechuri Venkat , Jain Manmohan , Peddireddi Venkata Sudhakar , Joshi Niranjan , Vijayan Shibu , Turaga Sanchit , Avasarala Vardhan
Published: October 2023

Analysing cough sounds is vital in pulmonary medicine. Recently, AI tools are being trained to analyse the acoustic signals of cough sounds so that more cases can be quickly tested, thereby reducing the patient load on primary healthcare systems. In this paper, we evaluate ”Swaasa”, our AI-based platform for rapid respiratory screening, highlighting its efficacy and ease of use. We applied our trained classifier to catch underlying pathologies from cough sound data collected from diverse sources. We then used a pattern classifier to identify specific respiratory conditions based on cough sound patterns. We tested the robustness of our methods by comparing our results with that of a pulmonary physician in 355 cases and show that Swaasa correctly predicted associated risk in 87.32% of those cases. Our platform has a sensitivity of 97.27% with a Positive Predictive Value (PPV) of 88.54%, giving us the potential to revolutionise disease screening, especially for large populations and in isolated rural areas. Our rapid and easy-to-use Software as a Service (SaaS) solution efficiently diagnoses and conserves resources, improves patient outcomes, and establishes a comprehensive and accessible healthcare framework.
Heterogeneous Nuclear Ribonucleoprotein C is an Indispensable Target in Acute Myeloid Leukemia
Authors: Vijay Vindhya , Meacham Amy , Katzell Lauren M. , Winer Aaron J. , Terrell Jesse , Archibald Vincent L. , Vaughn Lauren T. , Drusbosky Leylah , Thach Emily , Welmaker Greg , Giulianotti Marcello , Brothers Shaun , Beurel Eleonore , Bubenik Jodi L. , Swanson Maurice S. , Riva Alberto , Elsayed Abdelrahman H. , Lamba Jatinder K. , Cogle Christopher R.
Published: October 2023

Refractory disease is the greatest challenge in acute myeloid leukaemia (AML). Previously, we found vascular-associated AML cells as a source for refractory disease. In this study we use a bioassay of AML cells co-cultured on bone marrow-derived endothelial cells (BMECs) to screen 31 million compounds within a mixture-based synthetic combinatorial library followed by deconvolution leading to the identification of a novel polyamine sulfonamide that is selectively toxic to AML. Using three distinct proteomics methods we identified heterogeneous nuclear ribonucleoprotein C (HNRNPC) as the compound target.

Depleting HNRNPC reduces AML cell proliferation, viability, colony formation and fails to establish AML in mice. In contrast, no changes in cell proliferation, survival, or colony outgrowth were observed when depleting HNRNPC in normal hematopoietic or stromal cells. Clinical data show that lower HNRNPC expression independently associates with prolonged survival times in 554 adult and pediatric AML patients. We show that HNRNPC regulates DNA replication initiation and the Myc transcriptional program. Using differential isoform expression and differential alternative splicing analyses, we show significant alternative splicing of MAX after HNRNPC depletion, resulting in MAX transcript isoforms that lack Myc-interacting domains, which we term non-activating MAX isoforms. These Myc-interacting domains are necessary for the obligate heterodimerization of Myc and Max and are critical for Myc transcriptional activation. We further analyzed the alternative splicing landscapes of 538 AML patients and 33 specimens from healthy individuals and show substantial alternative splicing of mRNA in AML patients despite the absence of splicing factor gene mutations. Moreover, we found significantly high expression of non-activating MAX isoforms in healthy individuals, while AML patients highly expressed fully functional MAX isoforms, suggesting that MAX splicing may serve an important functional role in AML. Together, these data show HNRNPC as an indispensable splicing repressor in AML that is necessary for supporting deregulated Myc-Max activity and suggest HNRNPC as a potential therapeutic target for AML.
Investigating the Causal Role of Motor Brain Areas in Rhythm Reproduction: A Transcranial Direct Current Stimulation Study
Authors: Emerick Marina , Hoddinott Joshua , Grahn Jessica A.
Published: October 2023

Humans have an intrinsic tendency to move to music. However, our understanding of the neural mechanisms underlying the music-movement connection remains limited, and most studies have used correlational methods. Here, we used transcranial direct current stimulation (tDCS) to investigate the causal role of four brain regions commonly involved in movement timing and beat perception: the supplementary motor area (SMA), left and right premotor cortices (PMC), and the right cerebellum. On three different days, subjects received anodal, cathodal, or sham stimulation while reproducing strong-beat, weak-beat, and non-beat rhythms via finger tapping. Each subject only received stimulation in one of the four brain regions. As the SMA appears to play a primary role in beat perception, while the premotor cortex and cerebellum appear to have a more general role in timing, we predicted that the SMA stimulation would affect reproduction of rhythms with a beat, whereas premotor and cerebellar stimulation would affect reproduction of sequences with no beat. As expected, reproduction accuracy depended on beat strength; strong-beat rhythms were more accurately reproduced than weak and non-beat rhythms. Unexpectedly, tDCS had no effect on reproduction accuracy in any brain region. Thus, we found no evidence that modulating brain excitability in SMA, PMC, or cerebellum altered accuracy of rhythm reproduction. We discuss the implications of these results and future perspectives for this research.