bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal duration of oxaliplatin-based adjuvant chemotherapy in patients with different risk factors for stage II-III colon cancer: a meta-analysis
Authors: Kuang Ziyu , Wang Jiaxi , Liu Kexin , Wu Jingyuan , Li Jie
Published: February 2024

Background:

The duration of oxaliplatin–based chemotherapy in high–risk stage II, low–risk stage III, and high–risk stage III colon cancer patients is controversial. To reduce the risk of adverse events (AEs) without compromising efficacy while improving chemotherapy compliance is crucial.

Methods:

We searched Cochrane, Embase, Pubmed, and Web of Science databases for articles from inception to 2023.8.8, the main outcomes were disease–free survival, overall survival, chemotherapy completion rates, and AE frequency.

Results:

Six randomized controlled trials involving 10,332 patients were included. Disease–free survival analysis revealed that only the high–risk stage III colon cancer patients experienced better results with the six–month FOLFOX regimen when compared with the 3–month regimen (Hazard ratio [HR]: 1.32, 95% CI: 1.15–1.51, P<0.0001). Overall survival analysis revealed that extending the use of FOLFOX and CAPEOX regimens did not provide survival benefits for stage III colon cancer patients (HR: 1.16, 95% CI: 0.9–1.49, and HR: 0.89, 95% CI: 0.67–1.18, P=0.40). The completion rate of the three–month oxaliplatin–based adjuvant chemotherapy regimen was significantly higher than that of the six–month regimen (Relative risk [RR]: 1.16, 95% CI: 1.06–1.27, P=0.002). Moreover, the three–month regimen had significantly lower AE rates than the six–month regimen (RR: 0.62, 95% CI: 0.57–0.68, P<0.00001), with differences mainly concentrated in grade 3/4 neutropenia (RR: 0.70, 95% CI: 0.59–0.85, P=0.0002), peripheral sensory neuropathy at≥grade 2 (RR: 0.45, 95% CI: 0.38–0.53, P<0.00001), and hand–foot syndrome at≥grade 2 (RR: 0.36, 95% CI: 0.17–0.77, P=0.009).

Conclusions:

The six–month FOLFOX regimen should only be recommended for high–risk stage III colon cancer, while the three–month regimen can be recommended for other stages. A three–month CAPEOX regimen can be recommended for stage II–III colon cancer.
Relationship Between Childhood Sexual Abuse, Obesity, and Vulvodynia in Adulthood
Authors: Blaustein Rachel B. , Parker Christine A. , Haefner Hope K. , Reed Barbara D. , Haefner Jessica K. , Welch Kathryn C.
Published: February 2024

Objective

The aim of the study is to assess the relationship between childhood sexual abuse, obesity, and vulvodynia among adult women participating in a population-based longitudinal vulvodynia study.

Materials and Methods

Surveys assessed health status, diagnoses, risk factors, and screening test outcomes for women with vulvodynia. Associations between childhood sexual abuse (CSA) and obesity, CSA and vulvodynia, and obesity and vulvodynia were investigated. A multivariate model was used to determine if obesity mediates and/or modifies the relationship between CSA and vulvodynia.

Results

Of 2,277 women participating in the study, 1,647 completed survey data on CSA at 18 months, body mass index at 24 months, and vulvodynia over the first 54 months of the survey. Mean age was 50.9 ± 15.8 years. Overall, race and ethnicity were 77.4% White, 15.7% Black, 2.4% Hispanic, and 4.5% other. Five hundred thirty-nine participants (32.7%) were obese (body mass index >30) and 468 (28.4%) were overweight. Physical CSA before age of 18 years was reported by 20.0% (n = 329). During the study, 22.0% (n = 362) screened positive for vulvodynia on one or more surveys. After controlling for demographic variables, both obesity and screening positive for vulvodynia were associated with a history of CSA before age of 18 years (p = .013 and p < .001, respectively), but obesity was not associated with screening positive for vulvodynia (p = .865). In addition, multivariate analysis indicated no mediation of the CSA/vulvodynia relationship by obesity.

Conclusions

Although obesity and vulvodynia were independently associated with a history of CSA, obesity did not mediate or modify the relationship between CSA and vulvodynia in adulthood.
Uncovering Vulnerable Phases in Cochlear Implant Electrode Array Insertion: Insights from an In Vitro Model
Authors: Aebischer Philipp , Weder Stefan , Vischer Mattheus , Mantokoudis Georgios , Caversaccio Marco , Wimmer Wilhelm
Published: February 2024

Objectives

The aim of this study is to improve our understanding of the mechanics involved in the insertion of lateral wall cochlear implant electrode arrays.

Design

A series of 30 insertion experiments were conducted by three experienced surgeons. The experiments were carried out in a previously validated artificial temporal bone model according to established soft surgery guidelines. The use of an in vitro setup enabled us to comprehensively evaluate relevant parameters, such as insertion force, intracochlear pressure, and exact electrode array position in a controlled and repeatable environment.

Results

Our findings reveal that strong intracochlear pressure transients are more frequently caused during the second half of the insertion, and that regrasping the electrode array is a significant factor in this phenomenon. For choosing an optimal insertion speed, we show that it is crucial to balance slow movement to limit intracochlear stress with short duration to limit tremor-induced pressure spikes, challenging the common assumption that a slower insertion is inherently better. Furthermore, we found that intracochlear stress is affected by the order of execution of postinsertion steps, namely sealing the round window and posterior tympanotomy with autologous tissue and routing of the excess cable into the mastoid cavity. Finally, surgeons’ subjective estimates of physical parameters such as speed, smoothness, and resistance did not correlate with objectively assessed measures, highlighting that a thorough understanding of intracochlear mechanics is essential for an atraumatic implantation.

Conclusion

The results presented in this article allow us to formulate evidence-based surgical recommendations that may ultimately help to improve surgical outcome and hearing preservation in cochlear implant patients.
The HIV Open Call on Informed Consent and Ethics in Research (VOICE) for Adolescents and Young Adults: A Digital Crowdsourcing Open Call in Low- and Middle-Income Countries
Authors: Day Suzanne , Tahlil Kadija M. , Shah Sonam J. , Fidelak Lauren , Wilson Erin C. , Shah Seema K. , Nwaozuru Ucheoma , Chima Kelechi , Obiezu-Umeh Chisom , Chikwari Chido Dziva , Mwaturura Tinashe , Phiri Nomsa , Babatunde Abdulhammed Opeyemi , Gbajabiamila Titilola , Rennie Stuart , Iwelunmor Juliet , Ezechi Oliver , Tucker Joseph D.
Published: February 2024

Background

Many adolescents and young adults (AYAs; 10–24 years old) are excluded from HIV research because of social, ethical, and legal challenges with informed consent, resulting in limited AYA-focused data. We use a participatory approach to identify strategies for improving AYA consent processes in HIV research in low- and middle-income countries (LMICs).

Methods

We conducted a digital crowdsourcing open call for ideas to improve AYA consent to HIV research in LMICs. Crowdsourcing involves engaging a group of people in problem-solving, then sharing emergent solutions. Submissions were evaluated by 3 independent judges using predefined criteria, with exceptional strategies receiving prizes. Demographic data were collected, and textual data were qualitatively analyzed for emergent themes in barriers and facilitators for improving AYA consent in HIV research, guided by a socioecological model.

Results

We received 110 strategies total; 65 were eligible for evaluation, 25 of which were identified as finalists. Fifty-eight participants from 10 LMICs submitted the 65 eligible submissions, of which 30 (52%) were 18 to 24 years old. Thematic analysis identified 10 barriers to AYA consent, including HIV stigma, limited education, and legal/regulatory barriers. Strategies for improving AYA consent processes revealed 7 potential facilitators: enhancing AYA engagement in research, involving parents/guardians, improving education/awareness, improving institutional practices/policy, making research participation more AYA-friendly, enhancing engagement of other key communities of interest, and empowering AYA.

Conclusions

Diverse communities of interest in LMICs developed compelling strategies to enhance informed consent that may improve AYA inclusion in HIV research. These data will be used to develop practical guidance on improving AYA consent processes.
Using big data to understand interest in myopia
Authors: Nagra Manbir , Wolffsohn James S. , Ghorbani-Mojarrad Neema
Published: February 2024

SIGNIFICANCE

Popularity of publicly searched myopia terminologies is reported, for example, myopia control over myopia management and myopia over nearsighted or shortsighted. Insights are also provided for searches on specific myopia control interventions. The findings offer an evidence-based starting point for public messaging and communications by clinicians, policymakers, and other industry leaders.

PURPOSE

Public understanding of myopia can be difficult to ascertain for clinicians. Although small-scale studies provide valuable snapshots of data, findings tend to be population-specific and thus difficult to extrapolate to global audiences. In this study, big data were used to provide a more comprehensive depiction of global market interest in myopia.

METHODS

Google Trends data were used to analyze searches relating to myopia between January 2004 and August 2023. Data extracted were related to use of the terms myopia control and myopia management, with further searches executed for common myopia control interventions: orthokeratology, contact lenses, atropine, and glasses. Analysis into the search interest of other refractive error states, hyperopia and astigmatism, was also undertaken along with alternative terms that may be used to describe myopia. Where relevant, search trends were considered worldwide, by country, and over time.

RESULTS

Myopia was a more popular search term than common layman alternatives such as nearsighted or shortsighted. Myopia control was found to be more popular than myopia management, and of the specific myopia interventions, atropine was most popular. Compared with astigmatism and hyperopia, relative search volumes were greatest for myopia, on average accounting for approximately 50% of the relative search volume at the country level.

CONCLUSIONS

The differences identified in both popularity of myopia-related search terms and specific interventions may provide the basis for improvements in public messaging and facilitate patient-practitioner communication.
Switch to bictegravir/emtricitabine/tenofovir alafenamide from dolutegravir-based therapy
Authors: Orkin Chloe , Antinori Andrea , Rockstroh Jürgen K. , Moreno-Guillén Santiago , Martorell Claudia T. , Molina Jean-Michel , Lazzarin Adriano , Maggiolo Franco , Yazdanpanah Yazdan , Andreatta Kristen , Huang Hailin , Hindman Jason T. , Martin Hal , Pozniak Anton
Published: February 2024

Objective:

To evaluate the efficacy and safety of 96 weeks of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) treatment in participants switching from dolutegravir (DTG)-based therapy.

Design:

Studies 1489 (NCT02607930) and 1490 (NCT02607956) were phase 3 randomized, double-blind, active-controlled, first-line therapy trials in people with HIV-1. After 144 weeks of DTG-based or B/F/TAF treatment, participants could enter a 96-week open-label extension (OLE) of B/F/TAF.

Methods:

A pooled analysis evaluated viral suppression (HIV-1 RNA <50 copies/ml) and changes in CD4+ cell count at OLE Weeks 48 and 96, treatment-emergent resistance, safety, and tolerability after switch from a DTG-based regimen to B/F/TAF. Outcomes by prior treatment were summarized using descriptive statistics and compared by two-sided Wilcoxon rank sum test.

Results:

At OLE Week 96, participants who switched to B/F/TAF (N = 519) maintained high levels of virologic suppression (99.5 and 99.1% in those switching from DTG/abacavir/lamivudine and DTG+F/TAF, respectively) and CD4+ cell count, with no treatment-emergent resistance to B/F/TAF. Twenty-one participants experienced drug-related adverse events after switching, with diarrhea, weight gain, and headache occurring most commonly. There were no cases of proximal renal tubulopathy, drug-related Grade 4 adverse events, or serious adverse events. Two participants discontinued B/F/TAF due to treatment-related adverse events. Participants who switched from DTG/abacavir/lamivudine experienced statistically significant greater weight gain than those who switched from DTG+F/TAF; however, median weight change from the blinded phase baseline to OLE Week 96 was numerically similar across treatment groups.

Conclusion:

This medium-term analysis demonstrates the safety and efficacy of switching to B/F/TAF from a DTG-containing regimen in people with HIV-1.
Food Insecurity and Undernutrition Are Associated With Distinct Immunologic Profiles in People With Tuberculosis and Advanced HIV Starting Antiretroviral Therapy
Authors: Richterman Aaron , Sinha Pranay , Ivers Louise C. , Gross Robert , Rantleru Tumelo , Tamuhla Neo , Bisson Gregory P.
Published: February 2024

Background:

Food insecurity and undernutrition are related but distinct concepts contributing to poor HIV and tuberculosis outcomes. Pathways linking them with immunologic profile, which may relate to clinical outcomes, remain understudied.

Methods:

We analyzed data from a cohort study of 165 antiretroviral therapy (ART)–naïve adults with advanced HIV and newly diagnosed tuberculosis in Botswana from 2009 to 2013. Twenty-nine plasma biomarkers were measured pre-ART and 4 weeks post-ART initiation. We used principal components analysis (PCA) and multivariable linear regression models to assess relationships between immunological profiles and food insecurity (based on the Household Food Insecurity Access Scale), undernutrition (body mass index <18.5 kg/m2), and clinical outcomes.

Results:

PCA identified 5 principal components with eigenvalues >1. After adjustment, food insecurity was associated with PC3 pre-ART (0.19 per increased category of severity, 95% CI: 0.02 to 0.36) and post-ART (0.24, 95% CI: 0.07 to 0.41). PC3 was driven by higher levels of IFN-α, IFN-γ, interleukin (IL)-12p40, vascular endothelial growth factor, IL-1α, and IL-8 and decreased concentrations of IL-3. Undernutrition was associated with PC5 post-ART (0.49, 95% CI: 0.16 to 0.82). PC5 was driven by higher levels of IL-8, MIP-1α, IL-6, and IL-10 and decreased concentrations in IP-10 and IFN-α. Post-ART PC3 (4.3 percentage point increased risk per increased score of 1, 95% CI: 0.3 to 8.9) and post-ART PC5 (4.8, 95% CI: 0.6 to 8.9) were associated with death in adjusted models.

Discussion:

We identified 2 distinct immunologic profiles associated with food insecurity, undernutrition, and clinical outcomes in patients with advanced HIV and tuberculosis. Different pathophysiologic processes may link food insecurity and undernutrition with poor outcomes in this vulnerable patient population. Future studies should assess the impact of improving food access and intake on immune function and clinical outcomes.
Endoscopy for acute upper gastrointestinal bleeding: a protocol for systematic review and network meta-analysis of randomized controlled trials
Authors: Tang Xiaofang , Long Lixi , Wang Xiaoyun , Zhou Yiwu
Published: February 2024

Background:

Previous studies have reached mixed conclusions regarding the timing of endoscopic approaches for managing individuals with acute upper gastrointestinal bleeding (AUGIB). Therefore, the authors performed a protocol for systematic review and meta-analysis to assess the efficacy of various timing endoscopic approaches in managing individuals with AUGIB.

Methods:

The authors will search multiple databases, including PubMed, Embase, Web of Science, China National Knowledge Infrastructure, VIP Database, Wanfang Database, WHO International Clinical Trials Registry Platform, and Chinese Clinical Trial Register. The search will cover the entire duration, starting from the establishment of these databases until July 2023. The selection criteria will focus on randomized controlled trials that assess the efficacy of endoscopy with varying timing in managing patients with AUGIB. The primary outcomes will include primary hemostasis and inpatient death. The secondary outcomes will include recurrent bleeding, need for surgical intervention, admission to the ICU, blood transfusion needs, and duration of hospitalization. Two reviewers will select the studies, extract data, and assess the risk of bias. A Bayesian approach will be used to conduct a network meta-analysis.

Results:

The results of this systematic review and meta-analysis will be published in peer-reviewed journals.

Conclusion:

This network meta-analysis provides comprehensive evidence of different timing endoscopic approaches for managing individuals with AUGIB.
FABP4 as a Therapeutic Host Target Controlling SARS-CoV2 Infection
Authors: Baazim Hatoon , Koyuncu Emre , Tuncman Gürol , Burak M. Furkan , Merkel Lea , Bahour Nadine , Karabulut Ezgi Simay , Lee Grace Yankun , Hanifehnezhad Alireza , Karagoz Zehra Firat , Földes Katalin , Engin Ilayda , Erman Ayse Gokce , Oztop Sidika , Filazi Nazlican , Gul Buket , Ceylan Ahmet , Cinar Ozge Ozgenc , Can Fusun , Kim Hahn , Al-Hakeem Ali , Li Hui , Semerci Fatih , Lin Xihong , Yilmaz Erkan , Ergonul Onder , Ozkul Aykut , Hotamisligil Gökhan S.
Published: February 2024

Host metabolic fitness is a critical determinant of infectious disease outcomes. Obesity, aging, and other related metabolic disorders are recognized as high-risk disease modifiers for respiratory infections, including coronavirus infections, though the underlying mechanisms remain unknown. Our study highlights fatty acid-binding protein 4 (FABP4), a key regulator of metabolic dysfunction and inflammation, as a modulator of SARS-CoV-2 pathogenesis, correlating strongly with disease severity in COVID-19 patients. We demonstrate that loss of FABP4 function, by genetic or pharmacological means, reduces SARS-CoV2 replication and disrupts the formation of viral replication organelles in adipocytes and airway epithelial cells. Importantly, FABP4 inhibitor treatment of infected hamsters diminished lung viral titers, alleviated lung damage and reduced collagen deposition. These findings highlight the therapeutic potential of targeting host metabolism in limiting coronavirus replication and mitigating the pathogenesis of infection.
The effect of reactive balance training on responses to novel unexpected balance perturbations: a feasibility study
Authors: Huntley Andrew , Schinkel-Ivy Alison , Mansfield Avril
Published: February 2024

Trial design

Pilot study embedded within an assessor-blinded parallel randomized controlled trial.

Objective

To determine the feasibility of using unexpected and novel balance perturbations to assess the efficacy of reactive balance training.

Methods

Participants: Community-dwelling adults with chronic stroke who could walk independently without a gait aid for at least 10 m.Interventions: Reactive balance training, using manual and internal perturbations, or ‘traditional’ balance training (control group). Training took place for one hour per session, twice per week for six weeks.Outcome: Proportion of unexpected slips triggered as intended;state anxiety, perceptions of situations, and participants’ subjective responses to the unexpected slip perturbation; and spatiotemporal and kinematic features of unperturbed and perturbed walking (step length, width, and time, and mechanical stability) pre- and post-training.Randomisation: Blocked stratified randomization.Blinding: Assessors were blinded to group allocation.

Results

Numbers randomised: 28 participants were randomized (15 to reactive balance training, 13 to control). Of these, nine reactive balance training group participants and seven control participants were eligible and consented to additional data collection for the pilot study.Numbers analysed: 12 participants (six per group) completed the post-training unexpected slip data collection and were included in analysis of the pilot objective.Outcome: All unexpected slips triggered as intended.

Overall, participants did not report increased state anxiety or any concerns about the unexpected slip. Analysis of spatiotemporal and kinematic data suggested better stability following the unexpected slip for reactive balance trained participants than control participants; however, there were also between-group differences in spatiotemporal and kinematic features of walking pre- and post-training.

Conclusions

Unexpected slips are feasible in research. However, their value as outcomes in clinical trials may depend on ensuring the groups are balanced on prognostic factors.

Trial registration

ISRCTN05434601

Funding

Canadian Institutes of Health Research.
Enhanced testing can substantially improve defence against several types of respiratory virus pandemic
Authors: Petrie James , Hay James A. , Srimokla Oraya , Panovska-Griffiths Jasmina , Whittaker Charles , Masel Joanna
Published: February 2024

Mass testing to identify and isolate infected individuals is a promising approach for reducing harm from the next acute respiratory virus pandemic. It offers the prospect of averting hospitalizations and deaths whilst avoiding the need for indiscriminate social distancing measures. To understand scenarios where mass testing might or might not be a viable intervention, here we modelled how effectiveness depends both on characteristics of the pathogen (R0, time to peak viral load) and on the testing strategy (limit of detection, testing frequency, test turnaround time, adherence). We base time-dependent test sensitivity and time-dependent infectiousness on an underlying viral load trajectory model. We show that given moderately high public adherence, frequent testing can prevent as many transmissions as more costly interventions such as school or business closures. With very high adherence and fast, frequent, and sensitive testing, we show that most respiratory virus pandemics could be controlled with mass testing alone.
Influences on limited antimicrobial use in small-scale freshwater aquaculture farms in central Thailand
Authors: Alhusein Nour , Chantong Boonrat , Suwanpakdee Sarin , Wiratsudakul Anuwat , Gould Virginia C. , Wichuwaranan Kantima , Poonsawad Kornrawan , Montrivade Varapon , Charoenboon Nutcha , Sringernyuang Luechai , Avison Matthew B. , Lambert Helen , Sakcamduang Walasinee , Buller Henry , Reyher Kristen K.
Published: February 2024

Recent years have shown substantial growth both in the scale and the spread of freshwater aquaculture in Thailand, raising concerns about potential widespread antimicrobial use. This mixed-methods study used surveys and qualitative interviews to examine conditions of freshwater aquaculture farming in central Thailand in relation to animal health, disease management and patterns of antimicrobial use. Freshwater aquaculture in this area of Thailand was largely a domestic venture operated as a source of additional household income to increase financial security. Aquaculture was often integrated with other types of farming; initial outlay was reduced by repurposing unused crops, food, or animal manure (e.g. chicken droppings and pig dung) to fertilise aquaculture ponds. Among farmers representing twenty farms who were surveyed during 2019, only six farmers said they used antimicrobials. These included oxytetracycline, enrofloxacin, norfloxacin, ciprofloxacin and sulphonamides. Farmers doubted the benefits of using antimicrobials to treat aquatic animals; some believed antimicrobials stunted growth. The high cost of medicines and prohibitive regulations also discouraged antimicrobial use. Farmers linked disease occurrence to changes in the weather, the emergence of new diseases and variable water quality. They relied on farm management practices to maintain the health of their aquatic animals, using lime and salt to maintain and improve water quality and pH and to disinfect aquaculture pools. Farmers also reported obtaining juvenile fish and shrimp selectively from farms known to produce healthy stock. Specialised veterinary services for aquatic farming were rare, so farmers relied on their own experimentation with medicines, peer advice and recommendations of shopkeepers who sold both aquatic feed and medicines. This study unexpectedly reveals limited use of antimicrobials linked to socio-economic and ecological features of small-scale family aquaculture farms.
Recurrent and Concurrent Prediction of Longitudinal Progression of Stargardt Atrophy and Geographic Atrophy
Authors: Mishra Zubin , Wang Ziyuan , Xu Emily , Xu Sophia , Majid Iyad , Sadda SriniVas R. , Hu Zhihong Jewel
Published: February 2024

Stargardt disease and age-related macular degeneration are the leading causes of blindness in the juvenile and geriatric populations, respectively. The formation of atrophic regions of the macula is a hallmark of the end-stages of both diseases. The progression of these diseases is tracked using various imaging modalities, two of the most common being fundus autofluorescence (FAF) imaging and spectral-domain optical coherence tomography (SD-OCT). This study seeks to investigate the use of longitudinal FAF and SD-OCT imaging (month 0, month 6, month 12, and month 18) data for the predictive modelling of future atrophy in Stargardt and geographic atrophy. To achieve such an objective, we develop a set of novel deep convolutional neural networks enhanced with recurrent network units for longitudinal prediction and concurrent learning of ensemble network units (termed ReConNet) which take advantage of improved retinal layer features beyond the mean intensity features. Using FAF images, the neural network presented in this paper achieved mean (± standard deviation, SD) and median Dice coefficients of 0.895 (± 0.086) and 0.922 for Stargardt atrophy, and 0.864 (± 0.113) and 0.893 for geographic atrophy. Using SD-OCT images for Stargardt atrophy, the neural network achieved mean and median Dice coefficients of 0.882 (± 0.101) and 0.906, respectively. When predicting only the interval growth of the atrophic lesions with FAF images, mean (± SD) and median Dice coefficients of 0.557 (± 0.094) and 0.559 were achieved for Stargardt atrophy, and 0.612 (± 0.089) and 0.601 for geographic atrophy. The prediction performance in OCT images is comparably good to that using FAF which opens a new, more efficient, and practical door in the assessment of atrophy progression for clinical trials and retina clinics, beyond widely used FAF. These results are highly encouraging for a high-performance interval growth prediction when more frequent or longer-term longitudinal data are available in our clinics. This is a pressing task for our next step in ongoing research.
Prevalence of falls in the last weeks of life and relationship between falls, independence, and quality of dying: A secondary analysis of a large prospective cohort study
Authors: Otani Hiroyuki , Shimoinaba Junichi , Kashiwagi Hideyuki , Morita Tatsuya , Maeda Isseki , Yokomichi Naosuke , Hamano Jun , Yamaguchi Takashi , Mori Masanori
Published: February 2024

Objective

To determine the frequency of falls and their serious complications in palliative care units (PCUs), as well as explore the complex interplay between falls, independence, and quality of dying.

Methods

A secondary analysis of a large prospective cohort study of 23 PCUs in Japan was conducted from January 2017 to June 2018. Palliative care specialist physicians recorded whether patients experienced falls, serious complications from falls, activities that led to falls, independence (workability in the last days and use of indwelling urinary catheter), and Good Death Scale.

Results

Of the 1,633 patients evaluated, 9.2% (95% Confidence interval [95% CI 7.8 to 11]) experienced falls within 30 days prior to death. The patients who fell were mostly men, had eastern cooperative oncology group performance status 3 on admission, a longer estimated prognosis on admission, and delirium during hospitalization. Serious falls causing fractures or intracranial hemorrhages were rare (0.3% [95% CI 0.038 to 0.57]). The most common reason for falls was the need to use the toilet. The Good Death Scale and indwelling urinary catheter use were not significantly associated with falls.

Conclusion

Falls occur in approximately 10% of patients in PCUs, but serious complications are rare. The relationship between falls, independence, and quality of dying is complex; that is, a fall may not be necessarily bad, if it is the result of respect for the patient’s independence. Healthcare providers need to consider fall prevention while supporting patients’ desire to move on their own to maintain independence.

WHAT IS ALREADY KNOWN ON THIS TOPIC

Falls are a major healthcare concern because of their potential to cause physical harm, emotional distress, and increased healthcare costs.

Although many studies have investigated falls in acute care settings and the elderly population, there is a lack of literature specifically focusing on falls in the unique context of palliative care units.

WHAT THIS STUDY ADDS

Falls occur in only approximately 10% of patients, and only five cases (0.3%) of serious events were due to falls in palliative care units (PCUs).

Independence and quality of dying are not significantly compromised by falls.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

Although fall prevention is considered a priority, healthcare providers should support patients’ desires to move on their own to maintain independence.

It may be possible to maintain independence and quality of dying even for patients who have fallen.
Experiences of faculty and scientists with disabilities at academic institutions in the United States
Authors: Castro Franz , Cerilli Caroline , Hu Luanjiao , Iezzoni Lisa , Varadaraj Varshini , Swenor Bonnielin K.
Published: February 2024

Introduction

People with disabilities are underrepresented in higher education, facing systematic obstacles such as inaccessible institutions and difficulties in obtaining accommodations. This qualitative study aims to shed light on barriers to accessibility and disability inclusion in STEM and research institutions through confidential qualitative interviews with disabled faculty and scientists.

Methods

We recruited participants (via virtual flyers) working in the United States (U.S.) as research faculty or scientists that applied for grant funding (last five years), and self-identified as having a disability. Interviews (n=35) were conducted via semi-structured one-on-one live interviews or written interviews to accommodate participants’ needs. Data were analyzed by two study members using content analysis to identify themes and codes until saturation was reached.

Results

Themes included identity/visibility, career trajectories, accessibility, accommodations, bias, representation, and inclusion. Some participants reported not disclosing their disabilities at work or during hiring processes due to fear of negative perceptions from peers or potential employers. Experiences around stigma and bias were noted both in professional relationships and when interacting with disability service offices, underscoring difficulties and delays in processes to secure accommodations. Respondents highlighted the issues of lack of disability inclusion and low representation of people with disabilities in academia, elevating the importance of self-advocacy, and of role models and mentors in shaping career pathways for future researchers with disabilities.

Conclusion

Faculty with disabilities encounter systematic barriers at academic institutions, and lack of acknowledgement and research on these experiences has held back institutional and policy changes. To reduce disparities for disabled faculty, academic leadership must allocate resources to address ableism, create more inclusive environments, and raise standards beyond ADA compliance.
Cohort study of cardiovascular safety of different COVID-19 vaccination doses among 46 million English adults
Authors: Ip Samantha , North Teri-Louise , Torabi Fatemeh , Li Yangfan , Abbasizanjani Hoda , Akbari Ashley , Horne Elsie , Denholm Rachel , Keene Spencer , Denaxas Spiros , Banerjee Amitava , Khunti Kamlesh , Sudlow Cathie , Whiteley William N , Sterne Jonathan A C , Wood Angela M , Walker Venexia
Published: February 2024

Using longitudinal health records from 45.7 million adults in England followed for a year, our study compared the incidence of thrombotic and cardiovascular complications after first, second and booster doses of brands and combinations of COVID-19 vaccines used during the first two years of the UK vaccination program with the incidence before or without the corresponding vaccination. The incidence of common arterial thrombotic events (mainly acute myocardial infarction and ischaemic stroke) was generally lower after each vaccine dose, brand and combination. Similarly, the incidence of common venous thrombotic events, (mainly pulmonary embolism and lower limb deep venous thrombosis) was lower after vaccination. There was a higher incidence of previously reported rare harms after vaccination: vaccine-induced thrombotic thrombocytopenia after first ChAdOx1 vaccination, and myocarditis and pericarditis after first, second and transiently after booster mRNA vaccination (BNT-162b2 and mRNA-1273). These findings support the wide uptake of future COVID-19 vaccination programs.
Active Mutual Conjoint Estimation of Multiple Contrast Sensitivity Functions
Authors: Marticorena Dom CP , Wong Quinn Wai , Browning Jake , Wilbur Ken , Davey Pinakin , Seitz Aaron R. , Gardner Jacob R. , Barbour Dennis L.
Published: February 2024

Recent advances in nonparametric Contrast Sensitivity Function (CSF) estimation have yielded a new tradeoff between accuracy and efficiency not available to classical parametric estimators. An additional advantage of this new framework is the ability to independently tune multiple aspects of the estimator to seek further improvements. Machine Learning CSF (MLCSF) estimation with Gaussian processes allows for design optimization in the kernel, acquisition function and underlying task representation, to name a few. This paper describes a novel kernel for CSF estimation that is more flexible than a kernel based on strictly functional forms. Despite being more flexible, it can result in a more efficient estimator. Further, trial selection for data acquisition that is generalized beyond pure information gain can also improve estimator quality. Finally, introducing latent variable representations underlying general CSF shapes can enable simultaneous estimation of multiple CSFs, such as from different eyes, eccentricities or luminances. The conditions under which the new procedures perform better than previous nonparametric estimation procedures are presented and quantified.

Precis

Machine learning contrast sensitivity function estimation is improved by incorporation of additional information about the nature of the underlying and data from other eyes.
PheWAS analysis on large-scale biobank data with PheTK
Authors: Tran Tam C. , Schlueter David J. , Zeng Chenjie , Mo Huan , Carroll Robert J. , Denny Joshua C.
Published: February 2024

With the rapid growth of genetic data linked to electronic health record data in huge cohorts, large-scale phenome-wide association study (PheWAS), have become powerful discovery tools in biomedical research. PheWAS is an analysis method to study phenotype associations utilizing longitudinal electronic health record (EHR) data. Previous PheWAS packages were developed mostly in the days of smaller biobanks and with earlier PheWAS approaches. PheTK was designed to simplify analysis and efficiently handle biobank-scale data. PheTK uses multithreading and supports a full PheWAS workflow including extraction of data from OMOP databases and Hail matrix tables as well as PheWAS analysis for both phecode version 1.2 and phecodeX. Benchmarking results showed PheTK took 64% less time than the R PheWAS package to complete the same workflow. PheTK can be run locally or on cloud platforms such as theAll of UsResearcher Workbench (All of Us) or the UK Biobank (UKB) Research Analysis Platform (RAP).

Availability and implementation

The PheTK package is freely available on the Python Package Index (PyPi) and on GitHub under GNU Public License (GPL-3) athttps://github.com/nhgritctran/PheTK. It is implemented in Python and platform independent. The demonstration workspace forAll of Uswill be made available in the future as a featured workspace.

Contact

PheTK@mail.nih.gov
Tricuspid Valve Annulus Size by Echocardiography: Predictor of Cardiac Limitation in Pediatric Pectus Excavatum
Authors: Chang James , Eubanks James , Jancelewicz Tim , Joshi Vijaya , Martinez Hugo , Shah Samir , Paton Elizabeth , Philip Ranjit
Published: February 2024

Background

The severity of pectus excavatum (PEX) as measured by Haller index (HI) does not always correlate with symptoms of aerobic capacity. Transthoracic echocardiograms (TTE) are generally reported as normal which may influence the pediatrician’s decision to refer for corrective surgery. The aim of this study was to find a reproducible TTE marker as an indicator of right ventricular compression and compare it to severity of PEX and cardiopulmonary exercise test (CPET) indices.

Methods

The study included patients aged 10-19 years with an institution-based protocol for preoperative PEX evaluation with TTE, chest computed tomography (CT) for HI, and CPET from 2015-2021. We divided the patients into two groups, mild/moderate PEX (HI 2-3.5) and severe PEX (HI > 3.5). Tricuspid valve annulus size (TVAS) was compared between the groups as well as with other CPET and TTE indices using Student’s t-test. Spearman’s rank correlation coefficient was used to evaluate correlations between the severity of PEX by HI with the TTE and CPET parameters.

Results

Of the 124 patients, 82 (66.1%) had severe PEX and 42 (33.9%) had mild/moderate PEX. The mean TVAS z-scores in the mild/moderate PEX group was -1.98(SD 0.51) and -2.24 (SD 0.71) in the severe PEX group (p 0.046). There was a negative correlation between the TVAS z-score and the severity of PEX but this was not statistically significant (r = -0.154, p = 0.087). There was no significant difference in peak oxygen uptake (peak VO2) or left ventricular ejection fraction between the severity groups. However, the TVAS z-score positively correlated with peak VO2(median 43 ml/kg/min, r = 0.023, p = 0.01), peak VO2percent predicted (median 86%, r = 0.19, p = 0.04), and O2pulse (median 12.7 ml/beat, r = 0.20, p = 0.025), and negatively correlated with VE/VCO2(median 29, r = -0.23, p = 0.01).

Conclusion

The severity of PEX by HI does not factor in the location of cardiac compression and may not always reflect the degree of cardiac limitation. The Tricuspid valve annulus size is a good TTE indicator of cardiopulmonary compromise from PEX. A TVAS z score <-2 is a good predictor of cardiac compromise in pediatric PEX. This may provide additional functional parameters in the decision-making process for corrective surgery.
Phosphoketolase and KDPG aldolase metabolism modulate photosynthetic carbon yield in cyanobacteria
Authors: Xie Ningdong , Sharma Chetna , Rusche Katherine , Wang Xin
Published: February 2024

Cyanobacteria contribute to roughly a quarter of global net carbon fixation. During diel light/dark growth, dark respiration significantly lowers the overall photosynthetic carbon yield in cyanobacteria and other phototrophs. Currently, it is unclear how respiratory pathways participate in allocating carbon resources at night to optimize dark survival and support daytime photosynthesis. Here we show in the cyanobacteriumSynechococcus elongatusPCC 7942 that phosphoketolase is orchestrated in an integrative respiratory network in the dark to best allocate carbon resource for amino acid synthesis and prepare for photosynthesis reinitiation upon photoinduction. We further show that the respiratory Entner-Doudoroff (ED) pathway inS. elongatusis incomplete, with its key enzyme 2-keto-3-deoxy-6-phosphogluconate (KDPG) aldolase serving to modulate daytime photosynthesis through an alternative oxaloacetate decarboxylation activity. This activity allows for the bypassing of the tricarboxylic acid (TCA) cycle when ATP/NADPH consumption for biosynthesis is excessive and imbalanced relative to their production by light reactions, thereby preventing relative NADPH accumulation and ensuring optimal photosynthetic carbon yield. Optimizing these metabolic processes offers new opportunities to enhance photosynthetic carbon yield in cyanobacteria and other photosynthetic organisms under diel light/dark cycles.
Compensatory mutations potentiate constructive neutral evolution by gene duplication
Authors: Després Philippe C , Dubé Alexandre K , Grenier Jordan , Picard Marie-Ève , Shi Rong , Landry Christian R
Published: February 2024

Protein functions generally depend on their assembly into complexes. During evolution, some complexes have transitioned from homomers encoded by a single gene to heteromers encoded by duplicate genes. This transition could occur without adaptive evolution through intermolecular compensatory mutations. Here, we experimentally duplicate and evolve an homodimeric enzyme to examine if and how this could happen. We identify hundreds of deleterious mutations that inactivate individual homodimers but produce functional enzymes when co-expressed as duplicated proteins that heterodimerize. The structure of one such heteromer reveals how both losses of function are buffered through the introduction of asymmetry in the complex that allows them to subfunctionalize. Constructive neutral evolution can thus occur by gene duplication followed by only one deleterious mutation per duplicate.

One sentence summary

Compensatory deleterious mutations entangle gene duplicates
Instantaneous change in hyphal diameter in basidiomycete fungi
Authors: Mazheika Igor , Voronko Oxana , Kolomiets Oxana , Kamzolkina Olga
Published: February 2024

Under certain conditions, fungi can rapidly change the size of their cells. For example, it is known that the cells of many yeast species under hyperosmosis instantly and reversibly shrink entirely, without plasmolysis, with a decrease in volume of up to 70%. There is evidence that filamentous fungi can also instantly change the diameter of their unspecialized hyphae. This property is fundamental but requires detailed study. In this large-scale study (involving more than 50,000 cells measured) using light microscopy, the ability of three unrelated basidiomycete species to rapidly change the diameter of their hyphae under various factors was analyzed. It was found that all three fungi respond similarly to moderate hyperosmotic shock or detergent treatment, shrinking by an average of 12–14% in diameter. However, inhibitors of actin assembly can cause either expansion or shrinkage of hyphae or have no effect on a fungus. These results, along with previously established features of the macroinvagination systems of the plasma membrane in basidiomycetes, are important for understanding the complex structural-protective physiological mechanisms responsible for the survival and continuous functioning of fungal cells in unstable environmental conditions.
Cell-based assays and comparative genomics revealed the conserved and hidden effects ofWolbachiaon insect sex determination
Authors: Arai Hiroshi , Herran Benjamin , Sugimoto Takafumi N. , Miyata Mai , Sasaki Tetsuhiko , Kageyama Daisuke
Published: February 2024

It is advantageous for maternally transmitted endosymbionts to skew the sex ratio of their hosts toward females. Some endosymbiotic bacteria such asWolbachiacause their insect hosts to exclusively produce female offspring through male killing or feminization. In some lepidopteran insects, male killing is achieved by affecting the sex-determining process in males, and a unique mechanism of male killing and its functional link with feminization have been implicated. However, comparative analysis of these phenotypes is often difficult because they have been analyzed in different host–symbiont systems and transinfection ofWolbachiaacross different hosts is often challenging. In this study, we demonstrated the effects of nineWolbachiastrains on the splicing of sex-determining genes in Lepidoptera by fixing the host genetic background using a cell culture system. Cell transinfection assays confirmed that three male killing-inducingWolbachiastrains and one feminization-inducingWolbachiastrain increased the female-type splicing products of the core sex-determining genesdoublesex,masculinizer, andzinc finger protein 2. RegardingWolbachiastrains that do not induce male killing/feminization, three had no effect on these sex-determining genes, whereas two strains induced female-type splicing ofmasculinizeranddoublesexbut notzinc finger protein 2. Comparative genomics confirmed that homologs ofoscar, theWolbachiagene responsible for male killing inOstrinia, were encoded by male killing/feminizingWolbachiastrains, but not by non-male killing/non-feminizing strains. These results demonstrated the conserved effects underlying male killing and feminization induced byoscar-bearingWolbachia, and suggested other potential mechanisms thatWolbachiamight employ to manipulate host sex.

IMPORTANCE

Arthropods commonly carry maternally transmitted microbial symbionts such asWolbachia. The lack of paternal transmission frequently led to the evolution of reproductive parasitism traits, namely the manipulation of host reproduction in favor of female hosts, substantiated by male killing and feminization. AlthoughWolbachiainduces these phenotypes in a wide range of insects, the underlying mechanisms, diversity, and commonality remain largely unclear. In this study, we used a combination of transinfection assays and comparative genomics to reveal the conserved effects of male killing and feminizingWolbachiastrains on lepidopteran sex determination. Furthermore, we demonstrated that some non-male killing/non-feminizingWolbachiastrains also have an inherent ability to influence sex determination, albeit in a different manner, suggesting the potential for multiple mechanisms to manipulate host sex. This study also implied the frequent evolution of host suppressors againstWolbachia-induced reproductive manipulation.
Micromolar fluoride contamination arising from glass NMR tubes and a simple solution for biomolecular applications
Authors: Matwani Khushboo , Cornish Jasmine , DeBenedictis Erika Alden , Heller Gabriella T.
Published: February 2024

Fluorine (19F) NMR is emerging as an invaluable analytical technique in chemistry, biochemistry, material science, and medicine, especially due to the inherent rarity of naturally occurring fluorine in biological, organic, and inorganic compounds. Thus, we were surprised to identify an unexpected peak in our19F NMR spectra, corresponding to free fluoride, which appears to leach out from various types of new and unused glass NMR tubes over the course of several hours. We quantified this contaminant to be at micromolar concentrations for typical NMR sample volumes across multiple glass types and brands. We find that this artefact is undetectable for samples prepared in quartz NMR tubes within the timeframes of our experiments. We also observed that pre-soaking new glass NMR tubes combined with rinsing removes this contamination below micromolar levels. Given the increasing popularity of19F NMR across a wide range of fields, the long collection times required for relaxation studies and samples of low concentrations, and the importance of avoiding contamination in all NMR experiments, we anticipate that our simple solution will be useful to biomolecular NMR spectroscopists.