bluuebunny/crossref_metadata_2025 huggingface dataset:
Dinor-12-oxo-phytodienoic acid conjugation with amino acids inhibits its phytohormone bioactivity in Marchantia polymorpha
Authors: Liang Wenting , Zamarreño Ángel M , Torres-Montilla Salvador , de la Torre Antonio , Totozafy Jean Chrisologue , Kaji Takuya , Ueda Minoru , Corso Massimiliano , García-Mina José M , Solano Roberto , Chini Andrea
Published: November 2024

Jasmonates (JAs) are important phytohormones that regulate plant tolerance to biotic and abiotic stresses, and developmental processes. Distinct JAs in different plant lineages activate a conserved signaling pathway that mediates these responses: dinor-12-oxo-phytodienoic acid (dn-OPDA) isomers in bryophytes and lycophytes, and JA-Ile in most vascular plants. In many cases, the final responses triggered by these phytohormones depend on the accumulation of specialized metabolites. To identify compounds regulated by the dn-OPDA pathway in the liverwort Marchantia polymorpha, untargeted metabolomic analyses were carried out in response to wounding, a stress that activates the dn-OPDA pathway. A previously unreported group of molecules was identified from these analyses: dn-OPDA-amino acid conjugates (dn-OPDA-aas). Their accumulation after wounding and herbivory was confirmed by targeted metabolic profiling in Marchantia and in all species in which we previously detected dn-iso-OPDA. Mutants in GRETCHEN-HAGEN 3A (MpGH3A) failed to accumulate dn-OPDA-aa conjugates and showed a constitutive activation of the OPDA pathway and increased resistance to herbivory. Our results show that dn-iso-OPDA bioactivity is reduced by amino acid conjugation. Therefore, JA conjugation in land plants plays dichotomous roles: jasmonic acid conjugation with isoleucine (Ile) produces the bioactive JA-Ile in tracheophytes, whereas conjugation of dn-iso-OPDA with different amino acids deactivates the phytohormone in bryophytes and lycophytes.
Impact of the COVID-19 pandemic on participants in pragmatic clinical trials for chronic pain: implications for trial outcomes and beyond
Authors: Sellinger John J , Gilstad-Hayden Kathryn , Lazar Christina , Seal Karen , Purcell Natalie , Burgess Diana J , Martino Steve , Heapy Alicia , Higgins Diana , Rosen Marc I
Published: November 2024

Objective

The COVID-19 pandemic had profound effects on society, including those living with chronic pain. This study sought to examine pandemic impacts on individuals enrolled in pragmatic clinical trials focused on nonpharmacological treatments for chronic pain.

Methods

We evaluated responses to a questionnaire on COVID-19 impacts that had been administered to participants (n=2024) during study enrollment in 3 pragmatic clinical trials for chronic pain treatment. All trials were part of the National Institutes of Health (NIH)–Department of Veterans Affairs (VA)–Department of Defense (DOD) Pain Management Collaboratory. COVID-19–related impacts on access to health care, mental health, finances, ability to meet basic needs, and social support were assessed.

Results

Pandemic impacts were found in all domains assessed, including access to health care, mental and emotional health, ability to meet basic needs, finances, and social support. Impacts varied by demographic and clinical characteristics. The participants most negatively impacted by the pandemic were younger, Black or Latino, female, more educated, and unemployed and had screened positive for depression. No impact differences were found with regard to alcohol use disorder screenings or a prior history of COVID-19. Higher levels of pain were associated with worse pandemic impacts, and negative impacts declined over time.

Conclusions

Negative impacts of the pandemic on individuals living with chronic pain cut across aspects of life that are also central to effective pain management, including access to health care, social support, and mental and emotional health, with differential impacts found across key demographic and clinical factors. These findings should yield consideration of pandemic impacts in clinical practice and as moderating effects of treatment outcomes in clinical trials conducted during the pandemic.
Screening, brief intervention, and referral to treatment for pain management for veterans separating from military service: study protocol of a hybrid type 2 study testing implementation facilitation versus training-as-usual
Authors: Sellinger John J , Rosen Marc I , Lazar Christina M , Gilstad-Hayden Kathryn , Dziura James , Li Fang-Yong , Mattocks Kristin , Weede Adrienne , Sullivan-Tibbs Michael , Rose Liam , Garcia Vassallo Gabriela , Manhapra Ajay , Turner Amos , Vogt Dawne , Woodward Eva N , Hartmann Christine W , Haskell Sally G , Mohammad Amir , Martino Steve
Published: November 2024

Background

Veterans transitioning to civilian life often have chronic pain from service-related musculoskeletal disorders (MSD) with higher risk for substance misuse. Many seek VA (Department of Veterans Affairs) compensation for MSD. Use of Screening, Brief Intervention, and Referral to Treatment for Pain Management (SBIRT-PM) by VA Post-9/11 Military2VA (M2VA) case managers presents an opportunity to engage these veterans in VA pain care and address substance misuse. Implementation facilitation might help case managers use SBIRT-PM and engage veterans in services to improve outcomes.

Design

This study is a 2-cohort multisite cluster-randomized hybrid type 2 effectiveness-implementation trial. Within 2 separate cohorts of 14 VA sites each, sites will be allocated to receive an implementation strategy through the use of a constrained randomization procedure: virtual implementation facilitation or training-as-usual. Sites and M2VA case managers will receive the assigned implementation strategy to support use of SBIRT-PM. Recently discharged veterans (n = 1848) claiming service-connected MSD will be recruited, with case managers blind to veterans’ study enrollment. The proportion of participants who receive any SBIRT-PM will be the primary implementation outcome. Veteran participants will complete baseline, 12-week, and 36-week assessments, irrespective of whether case managers conduct SBIRT-PM with them (intent-to-treat). Pain intensity and interference will be the primary clinical outcomes. The study emphasizes pragmatic over explanatory methodological features.

This pragmatic trial will examine implementation facilitation versus training-as-usual in implementing SBIRT-PM to promote veteran engagement in nonpharmacological pain services. Using innovative methods to train and support VA case managers in SBIRT-PM, study outcomes could have broad implications for case management systems of care across the VA.
The implementation of a pain navigator program in the department of Veterans Affairs' (VA) health care systems: a cluster randomized pragmatic clinical trial
Authors: France Courtni , Cook Chad E , Coffman Cynthia J , Tumminello Christa , Choate Ashley , George Steven Z , Lentz Trevor A , Hastings Susan N
Published: November 2024

Objective

This manuscript describes the uptake of the AIM-Back Pain Navigator Pathway (PNP) designed to encourage use of non-pharmacologic care options within the Veterans Health Administration (VHA).

Design

This manuscript describes the implementation of a telehealth intervention from one arm of a multisite, embedded, cluster-randomized pragmatic trial comparing the effectiveness of two novel clinical care pathways that provide access to non-pharmacologic care for Veterans with low back pain (LBP).

Setting

Ten VHA clinics

Subjects

19 pain navigators, >200 primary care physicians, and over 1000 Veterans were involved in the PNP implementation

Methods

Data were generated within the VHA electronic health record (EHR) for the ongoing AIM-Back trial to describe PNP implementation for system-level findings in terms of number of visits, and type of care received

Results

Over a 3-year period, 9 of 10 clinics implemented the PNP within the context of the AIM-Back trial. The most frequent care recommended in the PNP included physical therapy, chiropractic, acupuncture, and yoga/tai chi. During follow-up at six-weeks, ∼50% of Veterans elected to receive a different care choice than what was initially prescribed. Notable variation across clinics was documented for PNP based on time to initiation of care and follow-up rates.

Conclusions

Implementation of the telehealth delivered PNP provides a nuanced understanding of the introduction of novel care programs within diverse clinical settings. These findings are most applicable to care programs that are delivered remotely and involve facilitation of existing care options.
Tele-collaborative outreach to rural patients with chronic pain: pragmatic effectiveness trial protocol for the CORPs study
Authors: Morasco Benjamin J , Pal Natassja , Ono Sarah S , McPherson Sterling M , Lynch Frances L , Dickerson John F , Dobscha Steven K , Krebs Erin E , Makris Una E , Mixon Amanda S , Maloy Patricia , Davis Melinda M , Lovejoy Travis I
Published: November 2024

Background

Despite the increased availability of evidence-based treatments for chronic pain, many patients in rural areas experience poor access to services. Patients receiving care through the VA may also need to navigate multiple systems of care.

Objective

To examine the effectiveness of a remotely delivered collaborative care intervention for improving pain interference among veterans with high-impact chronic pain living in rural areas.

Design

We will conduct a four-site pragmatic effectiveness trial of remotely delivered collaborative care for high-impact chronic pain. Participants (n = 608) will be randomized to the Tele-Collaborative Outreach to Rural Patients (CORPs) intervention or to minimally enhanced usual care (MEUC). Participants randomized to CORPs will complete a biopsychosocial assessment and five follow-up sessions with a nurse care manager (NCM), who will collaborate with a consulting clinician to provide personalized recommendations and care management. CORP participants will also be invited to a virtual 6-session pain education group class. Participants randomized to MEUC will receive a one-time education session with the NCM to review available pain services. All participants will complete quarterly research assessments for one year. The primary study outcome is pain interference. This trial will oversample veterans of female birth sex and minoritized race or ethnicity to test heterogeneity of treatment effects across these patient characteristics. We will conduct an implementation process evaluation and incremental cost-effectiveness analysis.

Discussion

This pragmatic trial will test the real-world effectiveness of a remotely delivered collaborative care intervention for chronic pain. Study findings will inform future implementation efforts to support potential uptake of the intervention.
Regional Differences in Job Satisfaction among Chinese Social Workers: The Mediating Effect of Attitudinal Professionalism
Authors: Tang Ning , Zhang Donghang , Sun Fei , Xia Yihong
Published: November 2024

Job satisfaction is a vital factor associated with better physical health and subjective well-being among social workers. This study aims to explore the job satisfaction of social workers from China’s Mainland and Macao and the role of attitudinal professionalism on regional differences. A cross-sectional survey collected data from 292 social workers in Mainland and 108 from Macao one year after the outbreak of COVID-19; 72 percent were female, less than half were married (44.8 percent), the average age was 32.64 years old, and the average working time was 6.07 years. Data were analyzed using descriptive statistics, independent t tests, and mediation analysis. Results indicated that Mainland social workers reported a significantly higher level of job satisfaction and attitudinal professionalism than Macao social workers. Moreover, attitudinal professionalism helped explain the regional difference in job satisfaction. The evidence from this study highlights the need to nurture professional beliefs and values among social workers, especially for Macao social workers, and also underscores the importance of developing continuing education programs to enhance social workers’ identification with and commitment to the profession. We also need to improve financial compensation and social status for Mainland social workers to sustain their professionalism.
Disparities in Buprenorphine Administration for Opioid Use Disorder in the Emergency Department
Authors: Koerber Samantha N. , Huynh David , Farrington Sydney , Springer Kylie , Manteuffel Jacob
Published: November 2024

Study Objective

Although buprenorphine is an effective treatment for opioid use disorder (OUD), this treatment is often not universally provided in the emergency department (ED). We aimed to determine whether patient characteristics, particularly race and ethnicity, were associated with buprenorphine administration.

Methods

This was a retrospective cross-sectional study of adult patients who had a positive screening result for opioid misuse in the ED at a single urban hospital. Univariate and multivariable logistic regressions were used to assess the association of patient characteristics (race, ethnicity, age, sex, insurance type, and Area Deprivation Index) with buprenorphine administration.

Results

Of 1082 patients who screened positive for opioid misuse, 133 (12%) were treated with buprenorphine and 949 (88%) were not. Despite representing over half the patient sample, Black patients (n = 682) were less likely than White patients (n = 310) to be treated with buprenorphine (multivariable: OR, 0.56; 95% CI, 0.35–0.88; P = 0.023). Age, sex, insurance type, ethnicity, and Area Deprivation Index were not associated with buprenorphine administration.

Conclusions

Patient race was associated with buprenorphine administration, even after controlling for multiple other social determinants of health. These data suggest racial disparities in care that should be investigated through further research to optimize equitable administration of buprenorphine.
Occipital Vascularized Bone Graft for Reconstruction of a C3-C7 Defect
Authors: Riasa I. Nyoman P. , Reece Edward M. , Mahadewa Tjokorda G. B. , Kawilarang Bertha , Jeger Jonathan L. , Awyono Steven , Putra Made Bhuwana , Putra Kevin Kristian , Suadnyana I. Putu Ramanda
Published: November 2024

The number of spinal reconstruction cases is growing, as are the accompanying complications. Wound complications after spinal reconstruction can be fatal and can affect up to 19% of patients undergoing major spine surgery. The discipline of spinoplastic surgery is characterized by the use of vascularized bone grafts to reconstruct spinal defects, which provide better results compared with nonvascularized and allogenic equivalents, owing to their superior blood supply. We present a 49-year-old man with spinal defect in the C3-C7 region treated with spinoplastic reconstruction. A 5 × 6 cm occipital VBG was designed with a centrally located muscular pedicle and successfully inset into the osseous defect. Radiographs taken 15 months postoperatively demonstrated overall excellent bony fusion, and the patient made an appropriate clinical recovery. In difficult spine procedures, the use of this occipital vascularized bone graft may lead to higher fusion rates without the need for free tissue transfer or allograft placement, which may not be available at all surgical centers around the world.
Enhanced Recovery Protocol Decreases Postoperative Opioid Use after Penile Inversion Vaginoplasty
Authors: Rios Sanchez Maria V. , Sanchez Figueroa Nicole , Zheng Eugene , Sotelo Leon Dan , Martinez-Jorge Jorys , Fahradyan Vahe
Published: November 2024

Background:

Penile inversion vaginoplasty (PIV) entails considerable soft-tissue dissection to the perineal region and involves complex tissue rearrangement. This study examines the role of an enhanced recovery after surgery (ERAS) pathway after PIV in reducing opioid use and controlling postoperative pain.

Methods:

A retrospective study of 50 transfemale patients who underwent PIV at a single institution from June 2021 to January 2023 was completed. The study compared 2 groups of patients who were given different postoperative pain management regimens: group A received standard postoperative analgesics and group B received ERAS. Variables such as postoperative pain scores on the numeric pain rating scale (0–10), use of opioid medication, length of hospital stay, and patient comorbidities were recorded and compared across the 2 groups.

Results:

The average hospital stay length was 4.92 (±0.85) days. Group A had a slightly longer average stay compared with group B. The average pain level in both groups was 4.25 (SD ±1.51). Group A exhibited a slightly higher average pain level of 4.31 (±1.53), whereas group B exhibited 4.16 (SD±1.51) (P = 0.77). Although pain levels did not significantly vary between the 2 groups, there was a statistically significant decrease in the amount of opioid medication used in group B with a P value of 0.009.

Conclusions:

ERAS protocol is effective in decreasing opioid usage in the immediate postoperative setting after PIV.
Influence of Mental Model-derived Themes on the Quality of Radiological Emergency Response by HAZMAT Technicians: Insights from a Case Study
Authors: Leek Angela E. , Keren Nir , Shelley Mack C. , Franke Warren , Mosher Gretchen A. , Simpson Stephen A. , Rice Timothy , Lawson Andrew
Published: November 2024

This paper investigates the link between gaps in emergency responders' notions of mental model regarding radiation and risk and their effectiveness in responding to radiological incidents. Particularly, this work focused on exploring themes that emerged in prior work related to improper understanding and application of knowledge concepts related to radiation risks and Radiological Dispersal Device (RDD) scenarios (Leek et al., 2024b). The research uses a quantitative approach to correlate various thematic elements, such as responders’ confidence levels, comprehension, and application of radiation risk principles, with the quality of the emergency response score gained through a virtual reality simulation. The results underscore a strong effect of responders' confidence level on response quality scores. Additionally, the study identifies that improper understanding of knowledge concepts and incorrect application of radiation risk and RDD concepts are factors that detract from the quality of response, especially the tendency to overestimate health risks associated with a 25-rem (0,25 Sv) dose and to misapply principles of radiation risk. The implications of this research are significant for the development and refinement of training programs for hazardous materials (HAZMAT) technicians and other emergency responders. The findings suggest the need for a comprehensive review of current training methodologies to address the identified deficiencies that had impacts on the quality of response. The findings provide a foundation for reshaping training priorities and operational readiness, driving the development of training that is both grounded in empirical evidence and that directly addresses the knowledge gaps influencing response quality. The methodological framework developed and employed, including the quality scoring system and the Expected Mental Model State (EMMS) Diagnostic Matrix, also hold potential for broader application in future investigations, extending to diverse types of responders and emergency scenarios.
Knowledge and Adherence to Radiation Protection among Non-radiation Health Care Workers at Two Operating Theatres in Windhoek, Namibia
Authors: Shivute Panduleni , Shilumba Moneni
Published: November 2024

Background: In operating theatres, diagnostic radiography is used to capture images during surgical operations. With the growing use of fluoroscopy, there are concerns about increased radiation exposure to healthcare workers such as doctors and nurses. Thus, assessing HCWs’ knowledge and adherence to radiation protection is crucial to prevent overexposure, radiation-related health issues, and ensure patient safety. Objective:The study aimed to assess the knowledge of non-radiation HCWs regarding radiation protection and determine the level of adherence to radiation protection in two theaters. Methods: A quantitative descriptive research methodology was used. Data collection involved a questionnaire, and participants were selected through a simple random sampling method. Data were analyzed using SPSS version 26. Results: Fifty-eight non-radiation HCWs participated. Most (77.6%) were female with nurses comprising the largest demographic (62.1%). Most participants (53.4%) lacked prior education in radiation protection. Concerningly, 70.7% did not use dosimeters during theater radiography, which is a requirement for radiation protection. No significant association was found between participants’ allocated hospital and the level of knowledge, but a significant association (p = 0.027) was found between participants’ allocated hospital and adherence levels. Conclusion: The findings suggest inadequate knowledge and adherence to radiation protection. Therefore, education on radiation protection must be mandated, and measures should be taken to enforce adherence.
Cariprazine and Cognition in Patients with Schizophrenia and Bipolar Disorder: A Systematic Review
Authors: García-Fernández Lorena , Romero-Ferreiro Verónica , Peñuelas-Calvo Inmaculada , Álvarez-Mon Miguel A. , Scala Mauro , Romero-Ferreiro Carmen , López Estela Jiménez , Santos José Luis , Rodriguez-Jimenez Roberto
Published: November 2024

Background

Cariprazine (CAR), an antipsychotic with partial agonism at the D3 receptor and higher affinity than dopamine, has shown significant procognitive effects in preclinical animal studies. This study systematically reviews CAR's effects on cognitive measures in patients with schizophrenia and bipolar disorder.

Methods

Two independent reviewers systematically searched PubMed, Web of Science, Scopus, and the Cochrane Library up to May 2024, following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Additional studies were found by hand searching the references of included studies. Eligible studies were randomized controlled trials (RCTs) in English that assessed CAR's effects on cognition in patients with schizophrenia or bipolar disorder. Quality was assessed using the Jadad scale.

Results

Out of 139 reports, 5 studies (involving 6,104 patients with schizophrenia or bipolar disorder) were included. In schizophrenia, CAR showed better cognitive outcomes (mainly indirect measures) than placebo (PBO) in both early and late stages. It also outperformed risperidone and aripiprazole in attention-related cognitive tests. In bipolar disorder, CAR improved cognition compared to PBO (also using indirect measures). Most studies found the greatest cognitive benefits with low doses of CAR (1.5–3 mg/d).

Conclusions

CAR improved cognitive measures compared to PBO and other D2 antagonists or partial agonists in RCTs, especially in patients with greater baseline impairment. Thus, CAR may be a promising option for enhancing cognition in schizophrenic and bipolar patients; though, more trials using specific cognitive assessment tools are needed.

Systematic review registration

PROSPERO CRD42023485028
Incorporating Lifestyle Medicine Into Occupational Medicine Practice
Authors: Hymel Pamela A. , Stave Gregg M. , Burton Wayne N. , Schultz Alyssa B. , Jones Nathan , Liva Jeffrey , Price Richard D. , Loeppke Ron , Stout Ronald , Saito Kenji ,   ACOEM Presidential Task Force on Lifestyle Medicine and OEM Practice
Published: November 2024

Lifestyle medicine (LM) utilizes evidence-based therapeutic lifestyle changes to address lifestyle factors that impact health, performance, and injury risk and recovery. By integrating LM principles into clinical care, workplace policies, and programs, along with other evidence-based methods, occupational and environmental medicine clinicians and medical directors can enhance worker health and performance, manage chronic disease, and facilitate faster recovery from injury and illness. This guidance addresses approaches that can be used in the clinic and workplace to address tobacco, substance misuse, nutrition, physical activity, overweight/obesity, sleep, mental well-being, and social connectedness.
Point-of-Care Ultrasound on Clinical Rotations: Reported Opportunity and Objective Number of Examinations
Authors: Breunig Michael , Kingsley Ryan , Yanambaka Shar , Kingsley Thomas
Published: November 2024

Introduction

Point-of-care ultrasound (POCUS) inclusion in physician assistant (PA) program curricula is increasing. Research has shown that preceptors' readiness to teach POCUS on rotations is limited. The purpose of this research is to describe PA students' self-reported opportunity to practice POCUS on rotations, to quantify the number of POCUS examinations completed on rotations, and to analyze data to provide insights into which rotations might be most amendable to POCUS training for PA students.

Methods

Students were surveyed about their preceptors' willingness to allow the practice of POCUS on rotations. Students were required to complete POCUS examinations during rotations. The number of examinations performed was extracted from the Butterfly Network software and paired with the students' rotation information. Descriptive statistics were completed.

Results

A survey response rate of 71.4% was noted. The student reported opportunities to practice POCUS were the highest on Family Medicine, Cardiology, Hospital Internal Medicine (HIM), and Emergency Medicine (EM). Students completed 778 POCUS examinations on rotations. A higher objective number of examinations were completed on EM and HIM rotations.

Discussion

EM and HIM rotations afforded the most opportunity to convert the reported opportunity to practice POCUS to the objective act of obtaining POCUS images. Most rotations had proportionally similar number of POCUS examinations completed per organ system, however, Cardiology had a disproportionately higher number of cardiac examinations. This rotation and application-specific understanding of PA students' ability to obtain POCUS examinations on rotations should be used by PA programs while developing POCUS curriculum.
Recent studies confirm the utility of the omega-3 index
Authors: Harris William S.
Published: November 2024

Purpose of review

The Omega-3 Index (O3I) was proposed 20 years ago as not only a marker of body omega-3 fatty acid status, but more importantly, as a risk factor for fatal coronary heart disease. The purpose of this review is to document the continued and growing use of this metric in nutrition research.

Recent findings

Of the 456 citations to the O3I in PubMed, 58 have appeared in the last 18 months. Several of these articles are reviewed, and they underscore the widespread use of the metric.

Although the O3I was originally developed in the cardiovascular field, it has since been used in the study of a remarkably large number of health conditions, all of which appear to be favorably impacted by higher levels of tissue omega-3 fatty acids as reflected by the O3I.
Variation in nutritional therapy practices: results of a survey on nutritional management of severe inflammatory bowel disease
Authors: Selin Katja Anneli , Andersson Sara , Bilén Katarina , Strid Hans , Björk Jan , Soop Mattias , Bresso Francesca , Hedin Charlotte R. H.
Published: November 2024

Objectives

The optimal nutritional management during a severe flare of inflammatory bowel disease is uncertain. The goal of this study was to describe variations in nutritional practices between different countries, professions and types of hospitals, as well as between ulcerative colitis (UC) and Crohn’s disease (CD).

Methods

In this cross-sectional study, a novel questionnaire was distributed in the ECCO Congress 2022 and via ECCO country representatives.

Results

The survey was completed by 313 participants. In total, 68% of the respondents were physicians. No specific nutritional screening tool was used by 45% of respondents. Almost a quarter of respondents reported less than 25% of patients being assessed by a dietitian in the first 3 days of a flare. The most common form of nutritional therapy was oral nutritional supplements (ONS) with easy-to-digest food. Total parenteral nutrition (TPN) was used by 10% of respondents for UC patients and 7% for CD. Energy intake, stool frequency and inflammatory biomarkers were the most common factors in determining when to change nutritional therapy. There were significant differences between different countries and health care professions for all the outcomes (P < 0.05). Nutritional management did not generally vary according to hospital type (university vs. general). During the first 3 days of a flare, a diet consisting exclusively of ONS was significantly more frequently used for CD than UC (P = 0.018). Otherwise, similar nutritional therapy strategies were reported for CD and UC, including using TPN to a similar extent.

Conclusion

There is significant variation in nutritional management practices. Country is the main determinant of differences in practice.
Gut microbiota in symptomatic uncomplicated diverticular disease stratifies by severity of abdominal pain
Authors: Tursi Antonio , Turroni Silvia , De Bastiani Rudi , Procaccianti Giorgia , D’Amico Federica , Allegretta Leonardo , Antonino Natale , Baldi Elisabetta , Casamassima Carlo , Casella Giovanni , Ciuffi Mario , De Bastiani Marco , Lazzarotto Lorenzo , Licci Claudio , Mancuso Maurizio , Penna Antonio , Pranzo Giuseppe , Sanna Guido , Tosetti Cesare , Zamparella Maria , Picchio Marcello
Published: November 2024

Objective

Patients with symptomatic uncomplicated diverticular disease (SUDD) may have a disrupted gut microbiota. However, current data are from small sample studies, and reported associations vary widely across studies. We aimed to profile the fecal microbiota in SUDD patients enrolled in primary care.

Methods

A retrospective study was conducted in SUDD (N = 72) and asymptomatic diverticulosis (AD) (N = 30), the latter serving as a control group.

Results

No significant differences in alpha and beta diversity were found between SUDD and AD, but SUDD was discriminated by a higher relative abundance of the family Streptococcaceae and the genera Alistipes, Agathobacter, and Butyricimonas. Interestingly, the gut microbiota of SUDD patients stratified by the severity of abdominal pain [according to the visual analog scale (VAS)]. In particular, higher diversity and health-associated taxa (such as Bifidobacterium, Eubacterium coprostanoligenes group, and Dorea) characterized mild (VAS score 1–3) SUDD, Proteobacteria, Veillonellaceae and Blautia moderate (VAS score 4–7) SUDD, and Prevotellaceae and Megasphaera severe (VAS score 8–10) SUDD.

Conclusion

Our analysis suggests that specific taxa may be related to SUDD, but the associations vary depending on the severity of abdominal pain. In addition to advancing our ecological understanding of this complex disease, our findings may pave the way for the incorporation of gut microbiota profiling into clinical practice to aid patient management, including stratification and treatment.
Prevalence of Syphilis Among Men Serving in the Militaries of Sub-Saharan Africa
Authors: Nabors Nicole L. , Tran Bonnie R. , Dapremont Lindsay , Tounouga Stephane , Dounia Adrinkaye Allao , Wando Ferdinand , Semu Yiheyis Aytenfisu , Kowo Joseph BN , Ngwata Gertrude , Mpassi Romain Bagamboula , Sevalie Stephen , Wiersma Steven T.
Published: November 2024

Background

The 2030 United Nations Agenda for Sustainable Development includes targets to end sexually transmitted infections (STIs) as a major public health threat. Prevalence data of STIs to inform strategies toward this goal are lacking in middle- and low-income countries, especially among men.

Methods

Data from Seroprevalence and Behavioral Epidemiology Risk Surveys conducted among militaries in Cameroon, Chad, Democratic Republic of the Congo (DRC), Ethiopia, Liberia, Malawi, Republic of the Congo, and Sierra Leone during 2013–2018 were used to estimate the prevalence of presumed active syphilis among active-duty military men. Associations of active syphilis infection with age, education, marital status, and rank for each country were assessed.

Results

The prevalence of active syphilis was less than 1% among men in Cameroon (2018), Ethiopia (2018), Liberia (2018), Malawi (2013), Republic of the Congo (2014), and Sierra Leone (2013). In Chad (2014), 6.2% (95% confidence interval, 5.2%–7.4%; n = 121/1949) of men tested positive for active syphilis. In DRC (2014), the prevalence of active syphilis was 15.5% (95% confidence interval, 14.1%–16.9%; n = 404/2611) among men. Active syphilis was associated with older age in DRC (P < 0.01), with less education in Chad (P = 0.03) and DRC (P < 0.01), and with rank in DRC (P = 0.048).

Conclusions

These data help address a paucity of information on prevalence of STIs in sub-Saharan Africa and demonstrate the need for improved surveillance among men.
Comparison of static balance and pressure distribution in individuals with unilateral lower limb amputation: The role of barefoot, heel support, and vision
Authors: Tatar Yaşar , Kablan Nilüfer , Gerçek Nejla , Alaca Nuray
Published: November 2024

Background:

In some cultures, shoes are not worn indoors. Prosthesis use barefoot can lead to pressure injuries and loss of balance due to abnormal residual limb loading.

Objective:

This study aimed to compare the effect of wearing standard alignment prostheses using barefoot at home and visual alteration on static balance and pressure distribution in individuals with unilateral transfemoral amputations (TFAs) or transtibial amputations (TTAs).

Study design:

Prospective parallel experimental study.

Methods:

Participants with unilateral TTAs (n = 44) and TFAs (n = 37) were included. Balance and load distribution were assessed using MatScan pressure platforms, both with a heel (3 × 2 cm2 area; 1.8 cm height) support (the use of shoes with a heel is mimicked) and barefoot.

Results:

Balance parameters were disrupted in all groups when eyes closed position (p < 0.05). Using heels reduced anterior-posterior and medial-lateral sway in TTA group during eyes closed (p < 0.05). When standing barefoot with the eye open position, TFA group had more load on the rear foot of the prosthetic foot and less load on the forefoot than TTA group (p < 0.05). The opposite pattern was observed in the intact foot (p < 0.05). Using heels in TTA group increased the load on the front of the intact side and the rear of the prosthetic side (p < 0.05).

Conclusion:

The balance parameters were impaired in both groups while standing barefoot in the absence of vision. However, using heel supports improved static balance in the TTA but not in the TFA group. Using heel support changed this load distribution in both groups, especially in the TTAs, and created positive changes.
Association Between Racial Marginalization with Direct Healthcare Expenditure, Time at Home and Rehabilitation Access Following Moderate to Severe Traumatic Brain Injury
Authors: Malhotra Armaan K , Nathens Avery B , Shakil Husain , Bondzi-Simpson Adom , Ribeiro Tiago , Essa Ahmad , He Yingshi , Witiw Christopher D. , Thorpe Kevin , Kulkarni Abhaya V , Wilson Jefferson R
Published: November 2024

Objective:

To determine the association between residence in racialized neighborhoods with direct healthcare expenditure and days at home (DAH) after moderate to severe traumatic brain injury (TBI).

Summary Background Data:

Differences in ethno-racial background have been associated with health outcome disparities. Much of this prior research was conducted in settings without universal healthcare coverage. The influence of ethno-racial background on health outcomes after TBI in universal healthcare settings remains unclear.

Methods:

This retrospective multicenter cohort study utilized linked administrative health data to identify adults sustaining moderate to severe TBI between 2009-2021. The primary exposure was an area-level index corresponding to the degree of racialized and immigrant populations within neighborhoods of residence (Q1-least racialized; Q5-most racialized). Co-primary outcomes were direct healthcare expenditure and DAH365days after injury. Secondary outcomes included discharge to rehabilitation and functional independence measure (FIM) scores at rehabilitation discharge.

Results:

6,188 patients met inclusion criteria. Patients in the most racialized neighborhoods incurred higher crude and adjusted direct healthcare costs compared to those in the least racialized neighborhoods. This effect was driven predominantly by physician claims and acute care costs. There were no significant differences in crude or adjusted DAH across quintiles. Access to rehabilitation and discharge FIM scores were comparable for patients residing different racialized neighborhood quintiles.

Conclusions:

Despite differences in healthcare expenditure, this study found similar home time, access to rehab and discharge FIM scores for TBI patients according to racialized neighborhood residence. Recognizing the limitations of area-level indices, our findings suggest equitable care delivery in a publicly funded universal care environment.
Risk of Recurrent Prolapse by Extent of Mesh Excision Procedures: A Multicenter Study
Authors: Sripad Abhishek A. , Gerjevic Kristen A. , Duong Vi , Hassani Daisy , Askew Amy , Glass Clark Stephanie , Woodburn Katherine L. , Maetzold Erin , Raker Christina A. , Rardin Charles R.
Published: November 2024

Importance

There is limited evidence guiding surgeons in how much mesh to resect when treating mesh complications.

Objective

The aim of the study was to compare rates of recurrent prolapse after mesh excisional surgical procedures for prolapse mesh complications.

Study Design

This multicenter, retrospective cohort study included patients, identified by Current Procedural Terminology codes, who were treated surgically for prolapse mesh complications at 8 institutions between 2010 and 2019. Excisional surgical procedures were categorized as major (total vaginal, extravaginal, and total mesh excisions) or minor (partial vaginal excisions and mesh revisions). The primary outcome was prolapse recurrence 1 year after mesh excision surgery. Secondary outcomes included long-term prolapse recurrence. Prolapse recurrence was evaluated by Kaplan-Meier survival analysis and Cox proportional hazards regression.

Results

Two hundred sixty-one patients met inclusion criteria with 188 (72%) undergoing minor and 73 (28%) major excisions, with a median follow-up time of 1.0 years. Groups differed in parity, location of implant surgery, and number of vaginal compartments involved in excision. Within the first year, major excisions had a higher prolapse recurrence rate (8.7%) than minor excisions (2.9%), P < 0.05. Adjusting for mesh implant type, the hazard ratio for pelvic organ prolapse was 6.1 in the major compared to minor excision. In the entire study period, prolapse recurrence was 33.8% and did not differ between groups.

Conclusions

Patients undergoing major excision surgical procedures may have higher rates of prolapse at 1 year compared to those undergoing minor excisions. However, in long-term follow-up, recurrence rates were not different. Our findings may aid surgeons in expectation setting prior to excisional procedures.
Functional framework of the kinetochore and spindle assembly checkpoint in Arabidopsis thaliana
Authors: Pettkó-Szandtner Aladár , Magyar Zoltán , Komaki Shinichiro
Published: November 2024

The kinetochore, critical for accurate chromosome segregation and genome stability in eukaryotes, comprises the Constitutive Centromere Associated Network (CCAN) and the KMN network. In animals, the CCAN associates with centromeric nucleosomes throughout the cell cycle, while the KMN network assembles at kinetochores during M phase, binding spindle microtubules and serving as a platform for the spindle assembly checkpoint (SAC) complex. Despite conserved functions, kinetochore components vary across organisms. This study investigates the subcellular localization and interaction maps of core kinetochore components inArabidopsis thaliana, finding that only CENP-C of the four conserved CCAN components localizes to kinetochores, while all KMN components consistently localize to the kinetochore throughout the cell cycle. Immunoprecipitation assays revealed interactions between core kinetochore proteins and regulators involved in DNA replication, histone modification, and chromatin remodeling, suggesting that the kinetochore may also function outside of M phase. Examining interactions between kinetochore and SAC components elucidates plant-specific SAC localization mechanisms providing a functional framework for understanding plant kinetochores and offering new insights into SAC regulation in plants.
Interpretable PROTAC degradation prediction with structure-informed deep ternary attention framework
Authors: Chen Zhenglu , Gu Chunbin , Tan Shuoyan , Wang Xiaorui , Li Yuquan , He Mutian , Lu Ruiqiang , Sun Shijia , Hsieh Chang-Yu , Yao Xiaojun , Liu Huanxiang , Heng Pheng-Ann
Published: November 2024

Proteolysis Targeting Chimeras (PROTACs) are heterobifunctional ligands that form ternary complexes with Protein Of Interests (POIs) and E3 ligases, exploiting the ubiquitin-proteasome system to degrade disease-causing proteins, promising to drug the undruggable. While PROTAC research primarily relies on costly and time-consuming wet experimental approaches, deep learning offers a promising avenue to accelerate development and reduce expenses. However, existing deep learning methods for PROTAC degradation prediction often overlook the significance of hierarchical molecular representation and protein structural information, hindering effective data modeling. Moreover, their black-box nature limits the interpretability of computational outcomes, failing to provide intuitive insights into substructure interactions within the PROTAC system. This study introduces PROTAC-STAN, a structure-informed deep ternary attention network (STAN) framework for interpretable PROTAC degradation prediction. PROTAC-STAN represents PROTAC molecules across atom, molecule, and property hierarchies and incorporates structure information for POIs and E3 ligases using a protein language model infused with structural data. Furthermore, it simulates interactions among three entities at the atom and amino acid levels via a novel ternary attention network tailored for the PROTAC system, enhancing interpretability. By integrating hierarchical PROTAC molecule representation, structural embedding of POI and E3 ligase, and ternary attention network modeling interactions, our approach substantially improves prediction accuracy by 10.95% while enabling significant model interpretability via atomic and residue level visualization of molecule and complex. Experiments on the refined public PROTAC dataset demonstrate that PROTAC-STAN outperforms state-of-the-art baselines in overall performance. The excellent performance of PROTAC-STAN is anticipated to establish it as a foundational tool in future research on PROTAC-related drugs, thereby accelerating the development of this field.
Natural Bacteriocins as Potential Drug Candidates Targeting Core Proteins in Mastitis Pathogens of Dairy Cattle
Authors: Hasnat Soharth , Rahman Md. Morshedur , Yeasmin Farzana , Jubair Mohammad , Helmy Yosra A. , Islam Tofazzal , Hoque M. Nazmul
Published: November 2024

Mastitis poses a major challenge in the dairy industry, with rising antibiotic-resistant strains underscoring the urgent need for alternative antimicrobial strategies. This study aimed to (i) identify essential core proteins in clinical mastitis (CM)-causing pathogens using genomic approach, and (ii) assess the efficacy of natural antimicrobial peptides as novel therapeutic agents targeting the selected core proteins for the rational management of mastitis in dairy cows. Through a core genomic analysis of 16 CM-causing pathogens, including strains ofStaphylococcus aureus, S. warneri,Streptococcus agalactiae,S. uberis,Escherichia coli,Klebsiella pneumoniae,Pseudomonas aeruginosa,P. putida, andP. asiatica, we identified 65 core proteins shared among these pathogens. Among them, ten proteins including PhoH, TrpB, FtsZ, HslV, HupB, RibH, InfA, MurA, GlxK, and Rho were found to be essential for the survival and virulence of these pathogens. Importantly, further novelty, resistance, and virulence assessments identified Rho and HupB as potential therapeutic targets. A comprehensive screening of 70 bacteriocin peptides (BPs) revealed 14 BPs that effectively interacted with both Rho and HupB proteins. Further analysis showed that BP8 and BP32 disrupt Rho protein function by blocking transcription termination process, while BP8, BP39, and BP40 prevent HupB from binding to DNA. These findings confirm the promising stability and efficacy of BP8 against both target proteins in CM-pathogens, highlighting it as a promising broad-spectrum therapeutic agent. Our computational study identified Rho and HupB as key proteins in CM-causing pathogens, which can be targeted by natural bacteriocins like BP8, suggesting its potential for developing effective and sustainable therapeutics against mastitis in dairy cattle.

Author Summary

Mastitis poses a significant threat to the global dairy industry, with rising antibiotic resistance necessitating alternative therapeutic strategies. This study identified essential core proteins in clinical mastitis-causing pathogens through a genomic approach and evaluated natural antimicrobial peptides (bacteriocins) as novel therapeutic agents. Through a core-genomic analysis, Rho and HupB were identified as key therapeutic targets. Bacteriocin peptides such as BP8 demonstrated promising efficacy by disrupting regular transcription termination process and DNA replication, offering a promising solution for next-generation mastitis therapies. The findings underscore the potential of BP8 as a sustainable, broad-spectrum antimicrobial agent, contributing to the rational management of mastitis in dairy cattle.
DrugProtAI: A guide to the future research of investigational target proteins
Authors: Halder Ankit , Samantaray Sabyasachi , Barbade Sahil , Gupta Aditya , Srivastava Sanjeeva
Published: November 2024

Drug design and development are central to clinical research, yet ninety percent of drugs fail to reach the clinic, often due to inappropriate selection of drug targets. Conventional methods for target identification lack precision and sensitivity. While various computational tools have been developed to predict the druggability of proteins, they often focus on limited subsets of the human proteome or rely solely on amino acid properties. To address the challenge of class imbalance between proteins with and without approved drugs, we propose a novel Partitioning Method. We evaluated the druggability potential of 20,273 reviewed human proteins, of which 2,636 have approved drugs. Our comprehensive analysis of 183 features, encompassing biophysical and sequence-derived properties, achieved a median AUC of 0.86 in target predictions. We utilize SHAP (Shapley Additive Explanations) scores to identify key predictors and interpret their contribution to druggability. We have reviewed and evaluated 688 investigational proteins from DrugBank (https://go.drugbank.com/) using our tool, DrugProtAI (https://drugprotai.pythonanywhere.com/). Our tool offers druggability predictions and access to 2M+ publications on drug targets and their effects, aiding in the selection of target proteins for drug development. We believe that insights into key predictors will significantly advance drug development and propel the field forward.