bluuebunny/crossref_metadata_2025 huggingface dataset:
Pulmonary, inflammatory, and oxidative effects of indoor nitrogen dioxide in patients with COPD
Authors: McHugh Erin G. , Grady Stephanie T. , Collins Christina M. , Moy Marilyn L. , Hart Jaime E. , Coull Brent A. , Schwartz Joel D. , Koutrakis Petros , Zhang J. , Garshick Eric
Published: October 2023

Introduction:

Indoor nitrogen dioxide (NO2) sources include gas heating, cooking, and infiltration from outdoors. Associations with pulmonary function, systemic inflammation, and oxidative stress in patients with chronic obstructive pulmonary disease (COPD) are uncertain.

Methods:

We recruited 144 COPD patients at the VA Boston Healthcare System between 2012 and 2017. In-home NO2 was measured using an Ogawa passive sampling badge for a week seasonally followed by measuring plasma biomarkers of systemic inflammation (C-reactive protein [CRP] and interleukin-6 [IL-6]), urinary oxidative stress biomarkers (8-hydroxy-2'deoxyguanosine [8-OHdG] and malondialdehyde [MDA]), and pre- and postbronchodilator spirometry. Linear mixed effects regression with a random intercept for each subject was used to assess associations with weekly NO2. Effect modification by COPD severity and by body mass index (BMI) was examined using multiplicative interaction terms and stratum-specific effect estimates.

Results:

Median (25%ile, 75%ile) concentration of indoor NO2 was 6.8 (4.4, 11.2) ppb. There were no associations observed between NO2 with CRP, 8-OHdG, or MDA. Although the confidence intervals were wide, there was a reduction in prebronchodilator FEV1 and FVC among participants with more severe COPD (FEV1: –17.36 mL; –58.35, 23.60 and FVC: –28.22 mL; –91.49, 35.07) that was greater than in patients with less severe COPD (FEV1: –1.64 mL; –24.80, 21.57 and FVC: –6.22 mL; –42.16, 29.71). In participants with a BMI <30, there was a reduction in FEV1 and FVC.

Conclusions:

Low-level indoor NO2 was not associated with systemic inflammation or oxidative stress. There was a suggestive association with reduced lung function among patients with more severe COPD and among patients with a lower BMI.
Development, validation, and clinical utility of a risk prediction model for recurrent preeclampsia
Authors: Zhang Lizi , Wang Weiwei , Gong Jingjin , Wang Xinghe , Liang Jingying , Gu Shifeng , Su Minglian , Bi Shilei , Sun Manna , Chen Jingsi , Zheng Weitan , Wu Junwei , Wang Zhijian , Liu Jianmeng , Li Hongtian , Chen Dunjin , Du Lili
Published: October 2023

Objectives:

We aim to establish a predictive model for recurrent preeclampsia.

Methods:

A retrospective review of medical records from three hospitals between 2010 and 2021 was conducted. The study included women who had two consecutive singleton deliveries at the same hospital, with the first delivery complicated by preeclampsia. A multivariable logistic regression model was constructed using a training cohort, and subsequently cross-validated and tested using an independent cohort. The model's performance was assessed in terms of discrimination and calibration, and its clinical utility was evaluated using decision curve analysis (DCA).

Results:

Among 296 405 deliveries, 694 women met the inclusion criteria, with 151 (21.8%) experiencing recurrent preeclampsia. The predictive model incorporated 10 risk factors from previous preeclampsia, including gestational weeks with elevated blood pressure, gestational diabetes mellitus (GDM), pericardial effusion, heart failure, limb edema, serum creatinine, white blood cell count, low platelet counts within one week before delivery, SBP on the first postpartum day, and postpartum antihypertensive use. Additionally, one risk factor from the index pregnancy was included, which was antihypertensive use before 20 weeks. The model demonstrated better discrimination, calibration, and a net benefit across a wide range of recurrent preeclampsia risk thresholds. Furthermore, the model has been translated into a clinical risk calculator, enabling clinicians to calculate individualized risks of recurrent preeclampsia.

Conclusion:

Our study demonstrates that a predictive tool utilizing routine clinical and laboratory factors can accurately estimate the risk of recurrent preeclampsia. This predictive model has the potential to facilitate shared decision-making by providing personalized and risk-stratified care.
Hypertension prevalence, coding and control in an urban primary care setting in the UK between 2014 and 2021
Authors: Basta Karol , Ledwaba-Chapman Lesedi , Dodhia Hiten , Ashworth Mark , Whitney David , Dalrymple Kathryn , Wang Yanzhong
Published: October 2023

Objective:

Hypertension is a leading preventable cause of mortality, yet high rates of undiagnosed and uncontrolled hypertension continue. The burden falls most heavily on some ethnic minorities and the socially deprived, with the COVID-19 pandemic having further widened inequalities. We sought to determine the prevalence and predictors of unmeasured blood pressure (BP), uncoded elevated BP and uncontrolled hypertension in primary care across 2014–2021.

Methods:

A population-based cohort study using data from all 41 general practices in a socioeconomically diverse inner-city borough. BP measurements, sociodemographic, lifestyle and clinical factors were extracted from anonymized primary care data. Hypertension and BP control were defined using NICE guidelines. Associations between patient characteristics and hypertension outcomes were identified using logistical regression modelling.

Results:

Of 549 082 patients, 39.5% had unmeasured BP; predictors included male sex [AOR 2.40, 95% confidence interval (95% CI) 2.26–2.43] and registration in the pandemic years. Of 71 970 adults with elevated BP, 36.0% were uncoded; predictors included obesity (AOR 2.51, 95% CI 2.42–2.60) and increasing age. Of 44 648 adults on the hypertension register, 46.8% had uncontrolled hypertension; predictors included black ethnicity compared to white (AOR 1.54, 95% CI 1.41–1.68) and cardiovascular co-morbidities (AOR 1.23, 95% CI 1.21–1.25). Social deprivation was only weakly or not significantly associated with hypertension outcomes.

Conclusion:

The burden of uncoded elevated BP and uncontrolled hypertension is high. Obesity and male sex were associated with uncoded elevated BP and uncontrolled hypertension. Black ethnicity was associated with uncontrolled hypertension. Initiatives are needed to optimize hypertension coding and control, with an emphasis on specific population subgroups.
Antihypertensive drug concentration measurement combined with personalized feedback in resistant hypertension: a randomized controlled trial
Authors: Peeters Laura E.J. , Kappers M.H.W. , Hesselink D.A. , van der Net J.B. , Hartong S.C.C. , van de Laar R. , Ezzahti M. , van de Ven P.J.G. , van der Meer I.M. , de Bruijne E.L.E. , Kroon A.A. , Indhirajanti-Tomasoa S. , van der Linde N.A.J. , Bahmany S. , Boersma E. , Massey E. K. , van Dijk L. , van Gelder T. , Koch Birgit C.P. , Versmissen Jorie
Published: October 2023

Background:

Adherence to antihypertensive drugs (AHDs) is crucial for controlling blood pressure (BP). We aimed to determine the effectiveness of measuring AHD concentrations using a dried blood spot (DBS) sampling method to identify nonadherence, combined with personalized feedback, in reducing resistant hypertension.

Methods:

We conducted a multicenter, randomized, controlled trial (RHYME-RCT, ICTRP NTR6914) in patients with established resistant hypertension. Patients were randomized to receive either an intervention with standard of care (SoC) or SoC alone. SoC consisted of BP measurement and DBS sampling at baseline, 3 months (t3), 6 months (t6), and 12 months (t12); AHD concentrations were measured but not reported in this arm. In the intervention arm, results on AHD concentrations were discussed during a personalized feedback conversation at baseline and t3. Study endpoints included the proportion of patients with RH and AHD adherence at t12.

Results:

Forty-nine patients were randomized to receive the intervention+SoC, and 51 were randomized to receive SoC alone. The proportion of adherent patients improved from 70.0 to 92.5% in the intervention+SoC arm (P = 0.008, n = 40) and remained the same in the SoC arm (71.4%, n = 42). The difference in adherence between the arms was statistically significant (P = 0.014). The prevalence of resistant hypertension decreased to 75.0% in the intervention+SoC arm (P < 0.001, n = 40) and 59.5% in the SoC arm (P < 0.001, n = 42) at t12; the difference between the arms was statistically nonsignificant (P = 0.14).

Conclusion:

Personalized feedback conversations based on DBS-derived AHD concentrations improved AHD adherence but did not reduce the prevalence of RH.
Home Health Agencies With High Quality of Patient Care Star Ratings Reduced Short-Term Hospitalization Rates and Increased Days Independently at Home
Authors: Li Jun
Published: October 2023

Background:

Critics argue that Medicare’s Quality of Patient Care home health star ratings are inaccurate. Valid ratings are essential to help patients find high-quality care.

Objective:

The aim of this study was to determine whether using the highest-rated home health agency available in a ZIP code improves outcomes.

Research Design:

A retrospective study of 1,870,080 Medicare fee-for-service beneficiaries using home health care from July 2015 through July 2016 in the United States. An instrumental variables approach is used to address the endogeneity of agency choice, where the instrument is the differential proximity of the patient to the closest highest-rated and closest lower-rated agency.

Outcomes:

Days independently at home; health care setting-specific days and death; hospitalization, emergency department use, and institutionalization risk.

Results:

Treatment by the highest-rated agencies available decreased risks (in percentage points) of hospitalization (−3.2; 95% CI, −4.1 to −2.3), emergency department use (−2.2; 95% CI, −3.2 to −1.1), and institutionalization (−0.9; 95% CI, −1.3 to −0.5) during the initial episode, and increased days independently at home by 2.6% or 3.75 (95% CI, 2.20–5.29) days in the 180 days after the end of the initial episode. Treatment effects were more pronounced for agencies that were above-average (6.51 d; 95% CI, 4.15–8.87), had ≥1 more star than the next-best agency (7.80 d; 95% CI, 4.13–11.47), and nonrural residents (4.57 d; 95% CI, 2.75–6.40). Effects were positive for both postacute (3.40; 95% CI, 1.80–5.00) and community-entry (5.60; 95% CI, 2.30–8.89) patients.

Conclusions:

Medicare’s Quality of Patient Care star rating correlates with reduced short-term hospitalizations and emergency department use and increased days independently at home in the longer term.
Evaluation of the Completeness of Managed Care Data to Identify Cancer Diagnoses and Treatments for Patients in the SEER-Medicare Data
Authors: Warren Joan L. , Parsons Helen M. , Mariotto Angela B. , Boyd Eric , Enewold Lindsey
Published: October 2023

Background:

The utility of codes on Medicare Advantage (MA) data to capture cancer diagnoses and treatment for cancer patients is unknown.

Objective:

This study compared cancer diagnoses and treatments on MA encounter data (MA data) with the Surveillance, Epidemiology, and End-Results (SEER) data.

Subjects:

Subjects were patients enrolled in either MA or Medicare fee-for-service (MFFS) when diagnosed with incident breast, colorectal, prostate, or lung cancer, 2015–2017, in a SEER cancer registry.

Measures:

MA data, from 2 months before to 12 months following SEER diagnosis, were reviewed to identify cancer diagnoses, surgery, chemotherapy, and radiotherapy (RT). MA data were compared with SEER to determine their sensitivity to capture cancer diagnoses and sensitivity/specificity to identify surgeries. The agreement between SEER and Medicare data regarding receipt of chemotherapy and RT was measured by Kappa statistics. A similar comparison to SEER diagnoses/treatments was made using MFFS claims to provide context for the SEER-MA comparison.

Results:

The study included 186,449 patients, 38% in MA. MA data had 92%+ sensitivity to identify SEER cancer diagnosis and 90%+ sensitivity for cancer surgery. Specificity for surgery was >84%, except for breast cancer (52%). Kappa statistics for agreement between SEER and MA data regarding chemotherapy varied by cancer, 0.61–0.82, and for receipt of RT exceeded 0.75 for all cancers. Results observed for MFFS claims were similar to those in MA data.

Conclusion:

For 4 common cancers, MA data included most cancer diagnoses and general types of cancer treatment reported in the SEER data. More research is needed to assess additional cancers and detailed treatments.
Intrapyloric Botulinum Toxin Injection for Refractory Nausea and Vomiting in Pediatric Patients
Authors: Osgood Peter T. , Essner Bonnie S. , Fountain Laura , Sullivan Erin C. , Meegan Carol , Fortunato John E.
Published: October 2023

Objectives:

Chronic nausea and vomiting may be associated with gastroparesis or other conditions. Poor mechanistic understanding of symptoms often precludes targeted therapy. Numerous case series suggest that intrapyloric botulinum toxin injection (IPBI) may be beneficial in treating gastroparesis and dyspepsia in children. We hypothesized that nausea, vomiting, and other symptoms, independent of gastroparesis, may improve with IPBI. We sought to identify gastric emptying (GE) and manometric patterns in IPBI responders versus nonresponders.

Methods:

Electronic records of 25 pediatric patients who received IPBI for refractory nausea, vomiting, or both were retrospectively reviewed. We assessed symptom improvement post-IPBI and compared symptoms, GE, and antroduodenal manometry (ADM) findings between IPBI responders and nonresponders.

Results:

At least one major symptom improved in 19 patients (76%) after IPBI. Of 22 patients completing a GE study, 14 had delayed GE with no significant difference between IPBI responders and nonresponders. Of 22 patients who underwent ADM, 18 had normal fasting peristalsis, 5 had postprandial antral hypomotility, 4 had neuropathic findings, and 19 had pylorospasm. IPBI responders, compared to nonresponders, demonstrated higher antral pressures with feeding (P < 0.0001) and shorter duration of pylorospasm (P = 0.0036). Antral pressures did not differ significantly with fasting or following motilin agonists.

Conclusions:

Our findings suggest that IPBI may have therapeutic benefit in pediatric patients with chronic nausea and/or vomiting, independent of gastroparesis. ADM findings of intact antral peristalsis and elevated antral pressures, in conjunction with efficacy of IPBI, support pyloric non-relaxation as a potential contributor to nausea and/or vomiting in pediatric patients.
Frequency of migraine and its associated triggers and relievers among medical students of Lahore: a cross-sectional study
Authors: Liaquat Amna , Sheikh Wahab Azmat , Yousaf Iram , Mumtaz Hassan , Zafar Maria , Khan Sherwani Aisha Haq
Published: October 2023

Introduction:

Headache is a widely prevalent illness that negatively impacts people’s lives, leaving them functionally incapable of performing regular everyday tasks. The global burden of headache is 40%, of which migraine accounts for 47%.

Objective:

This study aims to determine the frequency of migraine among medical students of Lahore and its characteristics, associated triggers, and relievers among medical students.

Methodology:

A cross-sectional study was conducted in medical colleges after obtaining ethical approval. Migraine was diagnosed using the criteria provided in the International Classification of Headache Disorders, Third Edition (ICHD-3), and data on triggers, relief, and demographics were collected. The information is analyzed using SPSS 22.

Result:

The data were collected from 522 medical students. The average age of the students was 21.3 ± 2.0 SD (in years). About 146 (28.0%) of the medical students have migraine according to ICHD-3 criteria and were diagnosed initially. Gender was insignificantly associated with migraine (P-value=0.32). Students with psoriasis, hypertension, and polycystic ovarian syndrome were statistically significantly related to migraines with a P-value=0.002. Dehydration is the most frequent aggravator, and adequate sleep is the most frequent reliever of migraine.

Conclusion:

The findings show a high frequency of migraine. They are similar in both genders, depicting that stressful lifestyles, inadequate sleep patterns, and bizarre dietary habits make them more prone to migraine episodes. So, further, detailed studies should be done on evaluating triggers and relievers of migraine and their interrelations with migraine so we can focus on preventive strategies, diagnosis, and treatment of migraine.
Promoting Nursing Student Mental Health Wellness
Authors: Stubin Catherine A. , Ruth-Sahd Lisa , Dahan Thomas A.
Published: October 2023

Background:

Being aware of elevated levels of student psychological distress by nursing faculty, and subsequently responding to it, may diminish nursing students’ experience of negative mental health well-being.

Purpose:

Relationships between perceived faculty support, resiliency, and the prevalence of depression, anxiety, and stress among undergraduate nursing students were explored.

Methods:

An exploratory mixed-methods design was used for this descriptive, cross-sectional study. The Depression, Anxiety, and Stress Scale-21, Brief Resilience Scale, Perceived Faculty Support Scale, a demographic questionnaire, and open-ended questions were used to collect data. A convenience sample of 989 undergraduate baccalaureate nursing students from across the United States completed the surveys.

Results:

Study results revealed resilience strategies and psychological and functional supportive faculty behaviors and actions are substantial predictors of lower depression, anxiety, and stress in undergraduate baccalaureate nursing students.

Conclusions:

Investments in faculty development to support nursing student resilience may reduce the degree of negative mental health well-being that students exhibit related to nursing education and promote their successful transition to nursing practice.
Navigating the Landscape: Barriers and Facilitators in Electronic Case Reporting Implementation Across Public Health Agencies
Authors: Hartsell Joel D. , Staes Catherine , Allen Katie S. , Dunn Angela C. , Wilson Fernando A. , Samore Matthew H. , Shoaf Kimberley
Published: October 2023

Objective:

The objectives were to identify barriers and facilitators for electronic case reporting (eCR) implementation associated with “organizational” and “people”-based knowledge/processes and to identify patterns across implementation stages to guide best practices for eCR implementation at public health agencies.

Design:

This qualitative study uses semistructured interviews with key stakeholders across 6 public health agencies. This study leveraged 2 conceptual frameworks for the development of the interview guide and initial codebook and the organization of the findings of thematic analysis.

Setting:

Interviews were conducted virtually with informants from public health agencies at varying stages of eCR implementation.

Participants:

Investigators aimed to enroll 3 participants from each participating public health agency, including an eCR lead, a technical lead, and a leadership informant.

Main Outcome Measure(s):

Patterns associated with barriers and facilitators across the eCR implementation stage.

Results:

Twenty-eight themes were identified throughout interviews with 16 informants representing 6 public health agencies at varying stages of implementation. While there was variation across these levels, 3 distinct patterns were identified, including themes that were described (1) solely as a barrier or facilitator for eCR implementation regardless of implementation stages, (2) as a barrier for those in the early stages but evolved into a facilitator for those in later stages, and (3) as facilitators that were unique to the late-stage implementation.

Conclusion:

This study elucidated critical national, organizational, and person-centric best practices for public health agencies. These included the importance of engagement with the national eCR team, integrated development teams, cross-pollination, and developing solutions with the broader public health mission in mind. While the implementation of eCR was the focus of this study, the findings are generalizable to the broader data modernization efforts within public health agencies.
Incidental FAPI Localization in Benign Bone Lesions in a Case of Carcinoma Stomach
Authors: Manda Divya , M V Manikandan , Suresh Arvind , Shukla Varun
Published: October 2023

Recently developed radiolabeled FAPI (fibroblast-activation protein inhibitors) have attracted researcher's attention in diagnosing various tumors because of its high specificity and better tumor-to-background ratio. Increasing use of 68Ga-FAPI PET/CT has resulted in reporting of incidental benign findings as well. We hereby present a case of suspected carcinoma stomach showing increased uptake in primary tumor in stomach as well as incidental uptake in benign subchondral cysts in bilateral shoulder joints and right hip joint on 68Ga-FAPI PET CT scan.
Complete Absence of FAPI Uptake in a Patient With Aggressive Diffuse Large B-Cell Lymphoma Involving Multiple Nodal and Extranodal Sites
Authors: Lu Li , Bin Ji
Published: October 2023

A 73-year-old man with histopathologically confirmed diffuse large B-cell lymphoma underwent both 18F-FDG and 18F-FAPI PET/CT. Although 18F-FDG PET showed abnormally increased tracer uptake in multiple nodal sites and organs, indicating the aggressiveness of the disease status, 18F-FAPI PET showed no obvious FAPI uptake in any of the FDG-avid lesions. Our case suggests that low expression of FAP in diffuse large B-cell lymphoma, as indicated by FAPI PET, might help determine a subgroup of patients with poorer outcome.
18F-FDG PET/CT Findings in Monkeypox Infection in an HIV Patient
Authors: Manzarbeitia-Arroba Begoña , Ruiz-Solis Sebastian , Vega-Perez Diana , Garcia-Alonso Pilar , Tabuenca Maria Jose
Published: October 2023

A 29-year-old man diagnosed with monkeypox infection underwent an 18F-FDG PET/CT for the study of organic involvement in the context of a nonsatisfactory clinical evolution. He had a history of HIV (with undetectable viral load). FDG PET/CT showed multiple hypermetabolic lymphadenopathies and bilateral pulmonary nodules with mild 18F-FDG uptake.
The Utility of Motor Evoked Potential Monitoring for Predicting Postoperative Motor Deficit in Patients With Insular Gliomas
Authors: Fan Xing , You Hao , Liu Jiajia , Tao Xiaorong , Wang Mingran , Li Ke , Yang Jun , Xie Jian , Qiao Hui
Published: October 2023

Purpose:

Motor evoked potential (MEP) monitoring has been widely applied in various neurosurgical operations. This study aimed to assess the predictive value of MEP monitoring for postoperative motor deficit (PMD) in patients with insular gliomas.

Methods:

Demographic and clinical data, MEP monitoring data, and follow-up data of 42 insular glioma patients were retrospectively reviewed, and 40 patients were finally enrolled. The value of MEP monitoring for predicting PMD was assessed with sensitivity, specificity, and false-positive/false-negative rates. Binary multivariate logistic regression analysis was performed to further identify the predictive value of MEP monitoring.

Results:

Statistical analysis showed that irreversible MEP changes, but not all MEP changes, were more effective in predicting PMD. The sensitivity and specificity of irreversible MEP changes for predicting long-term PMD were 85.71 and 93.94%, whereas the false-positive and -negative rates were 25.00 and 3.12% respectively. In addition, irreversible MEP changes were identified as the only independent predictor for long-term PMD (odds ratio, 101.714; 95% confidence interval, 6.001–1724.122; p = 0.001).

Conclusions:

MEP monitoring has been proven to be feasible in insular glioma surgery. Irreversible MEP changes showed good performance in predicting PMD. Their absence can offer an optimistic expectation for the long-term motor outcome. The findings can provide the surgical team with a more effective interpretation of MEP changes and contribute to exploring tailored MEP warning criteria.
Identification of Flavobacterium algoritolerans sp. nov. and Flavobacterium yafengii sp. nov., two novel members of the genus Flavobacterium
Authors: Yin Ce-Ce , Yang Lei-Lei , Xin Yu-Hua , Ye Jian , Liu Qing
Published: October 2023

Six psychrotolerant, Gram-stain-negative, aerobic bacterial strains, designated as LB1P51T, LB2P87T, LB2P84, LB3P48, LB3R18 and XS2P67, were isolated from glaciers on the Tibetan Plateau, PR China. The results of 16S rRNA gene analysis confirmed their classification within the genus

Flavobacterium

. Strain LB2P87T displayed the highest sequence similarity to

Flavobacterium sinopsychrotolerans

0533T (98.18 %), while strain LB1P51T exhibited the highest sequence similarity to

Flavobacterium glaciei

CGMCC 1.5380T (98.15 %). Strains LB2P87T and LB1P51T had genome sizes of 3.8 and 3.9 Mb, respectively, with DNA G+C contents of 34.2 and 34.1 %, respectively. Pairwise average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) calculations revealed that these strains represented two distinct species within the genus

Flavobacterium

. The results of phylogenomic analysis using 606 core genes indicated that the six strains formed a distinct clade and were most closely related to

F. glaciei

CGMCC 1.5380T. The ANI and dDDH values between the two species and other members of the genus

Flavobacterium

were below 90.3 and 40.1 %, respectively. Genome relatedness, the results of phylogenomic analysis and phenotypic characteristics collectively support the proposal of two novel species of the genus

Flavobacterium

: Flavobacterium algoritolerans sp. nov. (LB1P51T = CGMCC 1.11237T = NBRC 114813T) and Flavobacterium yafengii sp. nov. (LB2P87T = CGMCC 1.11249T = NBRC 114814T).
Mucosal Correlates of Protection after Influenza Viral Challenge of Vaccinated and Unvaccinated Healthy Volunteers
Authors: Bean Rachel , Giurgea Luca T. , Han Alison , Czajkowski Lindsay , Cervantes-Medina Adriana , Gouzoulis Monica , Mateja Allyson , Hunsberger Sally , Reed Susan , Athota Rani , Baus Holly Ann , Kash John C. , Park Jaekeun , Taubenberger Jeffery K. , Memoli Matthew J.
Published: October 2023

Induction of systemic antibody titers against hemagglutinin has long been the main focus of influenza vaccination strategies, but mucosal immunity has also been shown to play a key role in protection against respiratory viruses. By vaccinating and challenging healthy volunteers, we demonstrated that inactivated influenza vaccine (IIV) modestly reduced the rate of influenza while predominantly boosting serum antibody titers against hemagglutinin (HA) and HA stalk, a consequence of the low neuraminidase (NA) content of IIV and the intramuscular route of administration. Not surprisingly, viral challenge induced nasal and serum responses against both HA and NA. Correlations between mucosal IgA and serum IgG against specific antigens were low, whether before or after challenge, suggesting a compartmentalization of immune responses. Even so, volunteers who developed viral shedding for multiple days had lower baseline titers across both systemic and mucosal compartments as compared to those with no shedding or a single day of shedding. Regression analysis showed that pre-challenge HA inhibition titers were the most consistent correlate of protection across clinical outcomes combining shedding and symptoms, with NA inhibition titers and HA IgG levels only predicting the duration of shedding. Despite the inclusion of data from multiple binding and functional antibody assays against HA and NA performed on both serum and nasal samples, multivariate models were unable to account for the variability in outcomes, emphasizing our imperfect understanding of immune correlates in influenza and the importance of refining models with assessments of innate and cellular immune responses.

Importance

The devastating potential of influenza has been well known for over 100 years. Despite the development of vaccines since the middle of the twentieth century, influenza continues to be responsible for substantial global morbidity and mortality. To develop next-generation vaccines with enhanced effectiveness, we must synthesize our understanding of the complex immune mechanisms culminating in protection. Our study outlines the differences in immune responses to influenza vaccine and influenza infection, identifying potential gaps in vaccine-induced immunity, particularly at the level of the nasal mucosa. Furthermore, this research underscores the need to refine our imperfect models while recognizing potential pitfalls in past and future attempts to identify and measure correlates of protection.
Most users of a prenatal consultation dedicated to future fathers are immigrants facing hardship
Authors: Penot Pauline , Jacob Gaëlle , Guerizec Audrey , Trevisson Clotilde , Letembet Valérie-Anne , Harich Raya , Phuong Thomas , Renevier Bruno , Manuellan Pierre-Etienne , Desgrées du Loû Annabel ,   the Partage Study Group
Published: October 2023

Background

Prenatal care provides pregnant women with repeated opportunities for prevention, screening and diagnosis that have no current extension to future fathers. It also contributes to women’s general better access to health. The goal of PARTAGE study was to evaluate the level and determinants of adherence to a prenatal prevention consultation dedicated to men.

Methods

Between January 2021 and April 2022, we conducted a monocentric interventional study in Montreuil hospital. We assessed the acceptance of a prenatal prevention consultation newly offered to every future father, through their pregnant partner’s prior consent to provide their contact details.

Results

3,038 women provided contact information used to reach the fathers; effective contact was established with 2,516 men, of whom 1,333 (53%) came for prenatal prevention consultation. Immigrant men were more likely to come than French-born men (56% versus 49%, p < 0·001), and the more they faced social hardship, the more likely they were to accept the offer. In multivariate analysis, men born in Subsaharan Africa and Asia were twice as likely to attend the consultation as those born in Europe or North America.

Conclusion

Acceptance of this new offer was high. Moreover, this consultation was perceived by vulnerable immigrant men as an opportunity to integrate a healthcare system they would otherwise remain deprived of.

Trial Registration

https://classic.clinicaltrials.gov/ct2/show/NCT05085717
Pediatric Neural Changes to Physical and Emotional Pain After Intensive Interdisciplinary Pain Treatment: A Pilot Study
Authors: Lepping Rebecca J , Hoffart Cara M , Bruce Amanda S , Taylor Jasmine M , Mardis Neil J , Lim Seung-Lark , Wallace Dustin P
Published: October 2023

Brain areas activated during pain can contribute to enhancing or reducing the pain experience, showing a potential connection between chronic pain and the neural response to pain in adolescents and youth. This study examined changes in brain activation associated with experiencing physical pain, and the observation of physical and emotional pain in others, by using functional magnetic resonance imaging (fMRI) before and after intensive interdisciplinary pain treatment (IIPT). Eighteen youth (age 14 to 18) with widespread chronic pain completed fMRI testing before and after IIPT to assess changes in brain activation in response to physical and emotional pain. Broadly, brain activation changes were observed in frontal, somatosensory, and limbic regions. These changes suggest improvements in descending pain modulation via thalamus and caudate, and the different pattern of brain activation after treatment suggests better discrimination between physical and emotional pain. Brain activation changes were also correlated with improvements in clinical outcomes of catastrophizing (reduced activation in right caudate, right mid-cingulate, and postcentral gyrus) and pain-related disability (increased activation in precentral gyrus, left hippocampus, right middle occipital cortex, and left superior frontal gyrus). These changes support interpretation that reduced brain protective responses to pain were associated with treatment-related improvements. This pilot study highlights the need for larger trials designed to better understand the brain mechanisms involved in pediatric widespread pain treatment.

Perspective

This study examined changes in brain response to pain in youth experiencing chronic pain participating in intensive interdisciplinary pain treatment (IIPT). The novelty in this pilot study is the longitudinal neuroimaging findings in conjunction with established, clinically relevant behavioral and self-report measures of pain.
Representational Learning from Healthy Multi-Tissue Human RNA-seq Data such that Latent Space Arithmetics Extracts Disease Modules
Authors: de Weerd Hendrik A , Guala Dimitri , Gustafsson Mika , Synnergren Jane , Tegnér Jesper , Lubovac-Pilav Zelmina , Magnusson Rasmus
Published: October 2023

1

Developing computational analyses of transcriptomic data has dramatically improved our understanding of complex multifactorial diseases. However, such approaches are limited to small sample sets of disease-affected material, thus being sensitive to statistical biases and noise. Here, we ask if a variational autoencoder (VAE) trained on large groups of healthy, human RNA-seq data of multiple tissues can capture the fundamental healthy gene regulation system such that the learned representation generalizes to account for unseen disease changes. To this end, we trained a multi-scale representation to encode cellular processes ranging from cell types to genegene interactions. Importantly, we found that the learned healthy representations could predict unseen gene expression changes from 25 independent disease datasets. We extracted and decoded disease-specific signals from the VAE latent space to dissect this finding. Interestingly, the gene modules corresponding to this signal contained more disease-specific genes than the respective differential expression analysis in 20 of 25 cases. Finally, we matched genes related to the disease signals to known drug targets. We could extract sets of known and potential pharmaceutical candidates from this analysis and demonstrate the utility in three use cases. In summary, our study showcases how data-driven representation learning using a VAE as a foundational model allows an arithmetic deconstruction of the latent space such that biological insights enable the dissection of disease mechanisms and drug targets. Our model is available athttps://github.com/ddeweerd/VAE_Transcriptomics/.
Pulses of RhoA Signaling Stimulate Actin Polymerization and Flow in Protrusions to Drive Collective Cell Migration
Authors: Qian Weiyi , Yamaguchi Naoya , Lis Patrycja , Cammer Michael , Knaut Holger
Published: October 2023

In animals, cells often move as collectives to shape organs, close wounds, or—in the case of disease—metastasize. To accomplish this, cells need to generate force to propel themselves forward. The motility of singly migrating cells is driven largely by an interplay between Rho GTPase signaling and the actin network (Yamada and Sixt, 2019). Whether cells migrating as collectives use the same machinery for motility is unclear. Using the zebrafish posterior lateral line primordium as a model for collective cell migration, we find that active RhoA and myosin II cluster on the basal sides of the primordium cells and are required for primordium motility. Positive and negative feedbacks cause RhoA and myosin II activities to pulse. These pulses of RhoA signaling stimulate actin polymerization at the tip of the protrusions and myosin II-dependent actin flow and protrusion retraction at the base of the protrusions, and deform the basement membrane underneath the migrating primordium. This suggests that RhoA-induced actin flow on the basal sides of the cells constitutes the motor that pulls the primordium forward, a scenario that likely underlies collective migration in other—but not all (Bastock and Strutt, 2007; Lebreton and Casanova, 2013; Matthews et al., 2008)—contexts.
Wide Transition-State Ensemble as Key Component for Enzyme Catalysis
Authors: Jara Gabriel Ernesto , Pontiggia Francesco , Otten Renee , Agafonov Roman V. , Martí Marcelo A. , Kern Dorothee
Published: October 2023

Transition-state theory has provided the theoretical framework to explain the enormous rate accelerations of chemical reactions by enzymes. Given that proteins display large ensembles of conformations, unique transition states would pose a huge entropic bottleneck for enzyme catalysis. To shed light on this question, we studied the nature of the enzymatic transition state for the phosphoryl-transfer step in adenylate kinase by quantum-mechanics/molecular-mechanics calculations. We find a structurally wide set of energetically equivalent configurations that lie along the reaction coordinate and hence a broad transition-state ensemble (TSE). A conformationally delocalized ensemble, including asymmetric transition states, is rooted in the macroscopic nature of the enzyme. The computational results are buttressed by enzyme kinetics experiments that confirm the decrease of the entropy of activation predicted from such wide TSE. Transition-state ensembles as a key for efficient enzyme catalysis further boosts a unifying concept for protein folding and conformational transitions underlying protein function.
A Modular Design for Synthetic Membraneless Organelles Enables Compositional and Functional Control
Authors: Walls Mackenzie T. , Xu Ke , Brangwynne Clifford P. , Avalos José L.
Published: October 2023

Living cells organize a wide variety of processes through compartmentalization into membraneless organelles, known as biomolecular condensates. Given their ubiquitous presence across a wide spectrum of different organisms and cell types, biomolecular condensates are increasingly considered to offer great potential for biotechnological applications. However, native condensates remain difficult to harness for engineering applications, both due to their intertwined mechanisms of assembly and compositional control, and potential disruptions to native cellular processes. Here, we demonstrate a modular framework for the formation of synthetic condensates designed to decouple cluster formation and protein recruitment. Synthetic condensates are built through constitutive oligomerization of intrinsically-disordered regions (IDRs), which drive the formation of condensates whose composition can be independently defined through fused interaction domains. The composition of the proteins driven to partition into the condensate can be quantitatively described using a binding equilibrium model, demonstrating predictive control of how component expression levels and interaction affinity determine the degree of protein recruitment. Finally, the engineered system is utilized to regulate protein interactions and metabolic flux by harnessing the system’s compositional tunability.
Transcription factor stoichiometry, motif affinity and syntax regulate single-cell chromatin dynamics during fibroblast reprogramming to pluripotency
Authors: Nair Surag , Ameen Mohamed , Sundaram Laksshman , Pampari Anusri , Schreiber Jacob , Balsubramani Akshay , Wang Yu Xin , Burns David , Blau Helen M , Karakikes Ioannis , Wang Kevin C , Kundaje Anshul
Published: October 2023

Ectopic expression ofOCT4,SOX2,KLF4andMYC(OSKM) transforms differentiated cells into induced pluripotent stem cells. To refine our mechanistic understanding of reprogramming, especially during the early stages, we profiled chromatin accessibility and gene expression at single-cell resolution across a densely sampled time course of human fibroblast reprogramming. Using neural networks that map DNA sequence to ATAC-seq profiles at base-resolution, we annotated cell-state-specific predictive transcription factor (TF) motif syntax in regulatory elements, inferred affinity- and concentration-dependent dynamics of Tn5-bias corrected TF footprints, linked peaks to putative target genes, and elucidated rewiring of TF- to-gene cis-regulatory networks. Our models reveal that early in reprogramming, OSK, at supraphysiological concentrations, rapidly open transient regulatory elements by occupying non-canonical low-affinity binding sites. As OSK concentration falls, the accessibility of these transient elements decays as a function of motif affinity. We find that these OSK-dependent transient elements sequester the somatic TF AP-1. This redistribution is strongly associated with the silencing of fibroblast-specific genes within individual nuclei. Together, our integrated single-cell resource and models reveal insights into the cis-regulatory code of reprogramming at unprecedented resolution, connect TF stoichiometry and motif syntax to diversification of cell fate trajectories, and provide new perspectives on the dynamics and role of transient regulatory elements in somatic silencing.
Establishment and comparative genomics of a high-quality collection of mosquito-associated bacterial isolates - MosAIC (Mosquito-Associated Isolate Collection)
Authors: Foo Aidan , Brettell Laura E. , Nichols Holly L. ,   2022 UW-Madison Capstone in Microbiology Students, Medina Muñoz Miguel , Lysne Jessica A. , Dhokiya Vishaal , Hoque Ananya Ferdous , Brackney Doug E. , Caragata Eric P. , Hutchinson Michael , Jacobs-Lorena Marcelo , Lampe David J. , Martin Edwige , Valiente Moro Claire , Povelones Michael , Short Sarah M. , Steven Blaire , Xu Jiannong , Paustian Timothy D. , Rondon Michelle R. , Hughes Grant L. , Coon Kerri L. , Heinz Eva
Published: October 2023

Mosquitoes transmit medically important human pathogens, including viruses like dengue virus and parasites such asPlasmodiumspp., the causative agent of malaria. Mosquito microbiomes are critically important for the ability of mosquitoes to transmit disease-causing agents. However, while large collections of bacterial isolates and genomic data exist for vertebrate microbiomes, the vast majority of work in mosquitoes to date is based on 16S rRNA gene amplicon data that provides limited taxonomic resolution and no functional information. To address this gap and facilitate future studies using experimental microbiome manipulations, we generated a bacterialMosquito-Associated IsolateCollection (MosAIC) consisting of 392 bacterial isolates with extensive metadata and high-quality draft genome assemblies that are publicly available for use by the scientific community. MosAIC encompasses 142 species spanning 29 bacterial families, with members of theEnterobacteriaceaecomprising 40% of the collection. Phylogenomic analysis of three genera,Enterobacter, Serratia, andElizabethkingia, reveal lineages of mosquito-associated bacteria isolated from different mosquito species in multiple laboratories. Investigation into species’ pangenomes further reveals clusters of genes specific to these lineages, which are of interest for future work to identify functions underlying mosquito host association. Altogether, we describe the generation of a physical collection of mosquito-associated bacterial isolates, their genomic data, and analyses of selected groups in context of genome data from closely related isolates, providing a unique, highly valuable resource to investigate factors for bacterial colonisation and adaptation within mosquito hosts. Future efforts will expand the collection to include broader geographic and host species representation, especially from individuals collected from field populations, as well as other mosquito-associated microbes, including fungi, archaea, and protozoa.
Molecular logic of neuromodulatory systems in the zebrafish telencephalon
Authors: Anneser Lukas , Satou Chie , Hotz Hans-Rudolf , Friedrich Rainer W.
Published: October 2023

The function of neuronal networks is determined not only by synaptic connectivity but also by neuromodulatory systems that broadcast information via distributed connections and volume transmission. To understand the molecular constraints that organize neuromodulatory signaling in the telencephalon of adult zebrafish we used transcriptomics and additional approaches to delineate cell types, to determine their phylogenetic conservation, and to map the expression of marker genes at high granularity. The combinatorial expression of GPCRs and cell type markers indicates that all neuronal cell types are subject to modulation by multiple monoaminergic systems and distinct combinations of neuropeptides. Individual cell types were associated with multiple (typically >30) neuromodulatory signaling networks but expressed only a few diagnostic GPCRs at high levels, suggesting that different neuromodulatory systems act in combination albeit with unequal weights. These results provide a detailed map of cell types and brain areas in the zebrafish telencephalon, identify core components of neuromodulatory networks, highlight the cell type-specificity of neuropeptides and GPCRs, and begin to decipher the logic of combinatorial neuromodulation.
Compression of morbidity by interventions that steepen the survival curve
Authors: Yang Yifan , Mayo Avi , Levy Tomer , Raz Naveh , Jarosz Dan , Alon Uri
Published: October 2023

Longevity research aims to extend the period of healthy life, known as the healthspan, and to minimize the duration of disability and morbidity, known as the sickspan. Most longevity interventions in model organisms extend healthspan, but it is not known whether they extend healthspan relative to the lifespan - that is, whether they compress relative sickspan. Here, we present a theory that predicts which interventions effectively compress relative sickspan. The theory is based on the shape of the survival curve - the fraction of organisms surviving as a function of age. Interventions that extend mean lifespan while preserving the shape of the survival curve, known as scaling, are predicted to extend the sickspan proportionally, without compressing it. Such interventions include caloric restriction and many other longevity interventions. Conversely, a small subset of interventions that extend lifespan and steepen the shape of the survival curve, are predicted to compress the relative sickspan. We explain this based on the saturating removal mathematical model of aging, and present evidence from longitudinal health data in mice,Caenorhabditis elegansandDrosophila melanogaster. We discuss longevity interventions in mice that steepen the survival curves, including senolytics, ketogenic diet, and agents that reduce glucose spikes and protect blood vessels, as potential candidates for compressing the sickspan. We apply the theory to combinations of longevity interventions and discuss human healthspan data. This approach offers potential strategies for compressing morbidity and extending healthspan.
Structural characterization of the oligomerization of full-length Hantaan virus polymerase into symmetric dimers and hexamers
Authors: Trouilleton Quentin Durieux , Housset Dominique , Arragain Benoît , Malet Hélène
Published: October 2023

Hantaan virus is a dangerous human pathogen whose segmented negative-stranded RNA genome is replicated and transcribed by a virally-encoded multi-functional polymerase. Here we describe the complete cryo-electron microscopy structure of Hantaan virus polymerase in several oligomeric forms. Apo polymerase protomers can adopt two drastically different conformations, which assemble into two distinct homodimers, that can themselves gather to form hexamers.

Polymerase dimerization induces the stabilization of most polymerase domains, including the C-terminal region that notably contains a C-terminal domain that contribute the most to dimer’s interface, along with a lariat region that participates to the polymerase steadying.

Binding to viral RNA induces significant conformational changes resulting in oligomer disruption, suggesting the possible involvement of multimers as protecting systems that would stabilize the otherwise flexible C-terminal domains.

Overall, these results provide new insights into the multimerization capability of Hantavirus polymerase and may help to define antiviral compounds to counteract these life-threatening viruses.