bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrasound-guided erector spinae plane block for postoperative short-term outcomes in lumbar spine surgery: A meta-analysis and systematic review
Authors: Liu Hui , Zhu Jing , Wen Jing , Fu Qiang
Published: February 2023

Background:

Patients undergoing lumbar spine surgery usually suffer from moderate to severe acute pain. Erector spinae plane block (ESPB) has been applied to relieve acute pain in various surgeries and improve postoperative outcomes. This study aimed to further identify the efficacy and safety of erector spinae plane block in patients undergoing lumbar spine surgery. This study also evaluates the outcomes of the erector spinae plane block compared with other regional blocks.

Methods:

We searched PubMed, Web of Science, Cochrane library, Embase, and CINAHL databases to identify all randomized controlled trials evaluating the effects of ESPB on postoperative pain after lumbar spine surgery. The primary outcome is postoperative total opioid consumption in 24 hours. The secondary outcomes are postoperative pain scores, intraoperative opioid consumption, time to first rescue analgesia, number of patients requiring rescue analgesia, first time to ambulation after surgery, length of hospital stay, patients’ satisfaction score, and postoperative side effects such as postoperative nausea and vomiting, itching.

Results:

A total of 19 randomized controlled trials are included in the final analysis. Compared with no/sham block, ultrasound-guided erector spinae plane block can decrease perioperative opioid consumption including intraoperative opioid consumption: standardized mean difference (SMD) = −3.04, 95% confidence interval (CI) (−3.99, −2.09), P < .01, and opioid consumption postoperatively: (SMD = −2.80, 95% CI [−3.61, −2.00], P < .01); reduce postoperative pain at 2, 6, 12, 24, and 48 hours both at rest and movement; meanwhile shorten time to hospital length of stay: (SMD = −1.01, 95% CI [−1.72, 0.30], P = .006), decrease postoperative nausea and vomiting (RR = 0.35, 95% CI [0.27, 0.46], P < .00001), and improve patient satisfaction (SMD = −2.03, 95% CI [−0.96, 3.11], P = .0002). But ultrasound-guided ESPB doesn’t shorten the time to ambulation after surgery (SMD = −0.56, 95% CI [−1.21, 0.08], P = .09). Additionally, ESPB is not superior to other regional blocks (e.g., thoracolumbar interfascial plane/midtransverse process to pleura block).

Conclusion:

This meta-analysis demonstrates that ultrasound-guided ESPB can provide effective postoperative analgesia in patients undergoing lumbar spine surgery and improve postoperative outcomes, and it deserves to be recommended as an analgesic adjunct in patients undergoing lumbar spine surgeries.
Acute osteomyelitis of the patella due to Pseudomonas aeruginosa in an immunocompetent child: A case report
Authors: Kamiya Yasunari , Mishima Kenichi , Tanaka Tetsuji , Sawamura Kenta , Matsushita Masaki , Imagama Shiro
Published: February 2023

Rationale:

Plentiful vascularity and lack of the physis are thought to render the patella less vulnerable to osteomyelitis. Pseudomonas aeruginosa (PA) is an opportunistic pathogen predominantly affecting immunocompromised hosts. Despite the ubiquitous nature of PA, osteomyelitis of the patella caused by PA has been rarely reported in children.

Patient concerns:

A 5-year-old boy who had presented with a prolonged history of the left anterior knee pain following minor trauma was diagnosed with prepatellar bacterial cellulitis and bursitis. Afterward, a focal osteolytic lesion emerged at the ventral surface of the patella despite oral and intravenous antibiotic therapy lasting for weeks. We described clinical presentation as well as medical and surgical management of pediatric patellar osteomyelitis secondary to prepatellar septic bursitis.

Diagnoses:

Pseudomonas aeruginosa-associated osteomyelitis of the patella. Magnetic resonance imaging of the left knee showed a focal destructive change of the ventral half of the cartilaginous patella and a suprapatellar joint effusion. Bacterial culture from the bursa revealed Pseudomonas aeruginosa.

Interventions:

Systemic inflammation, patellar osteochondral destruction, and purulent synovial fluid of the knee were prolonged for 6 weeks despite antibiotics use deemed appropriate and reparative surgical debridement, whereas they were eventually resolved with a 6-week course of intravenous ceftazidime and cessation of continuous intracapsular irrigation.

Outcomes:

He was clinically asymptomatic at the latest follow-up but exhibited a minor leg length discrepancy <2 cm associated with overgrowth of the affected femur.

Lessons:

This is a rare case of Pseudomonas osteomyelitis of the patella in a healthy pediatric patient. Uncommon osteochondral sequelae occurred probably because of a protracted arthritis of the affected knee. We would like to emphasize the ineffectiveness of continuous irrigation without antibiotics for Pseudomonas aeruginosa-associated osteomyelitis.
Fatal posterior circulation stroke with persistent hiccups, sinus arrest and post-hiccup syncope: A case report
Authors: Zhang Na , Liang Hao , Wang Xibing , Wang Hong
Published: February 2023

Rationale:

Diagnosis of posterior circulation stoke is difficult, and magnetic resonance imaging especially diffusion-weighted imaging is superior to computed tomography. Persistent hiccups, sinus arrest, and post-hiccup syncope are extremely rare symptoms of posterior circulation stroke. However, there is no effective treatment for persistent hiccup.

Patient concern and diagnosis:

We describe a case of a 58-year-old hypertensive woman diagnosed with acute posterior circulation stroke who presented with persistent hiccups, sinus arrest, and post-hiccup syncope. Diffusion-weighted imaging revealed a high-intensity signal involving the left middle cerebellar peduncle and several spotted areas in the right occipital lobe.

Interventions:

Permanent pacemaker was implanted and metoclopramide was used to treat persistent hiccups.

Outcome:

The patient developed aspiration pneumonia and morbid dysphoria, and eventually died.

Lessons:

Posterior circulation stroke can cause cardiovascular and respiratory dysfunction. Consequently, physicians should pay more attention to posterior circulation lesions in patients with arrhythmia and syncope. An effective method to treat persistent hiccups is urgently needed.
The Relationship Between Depressive Symptoms, eHealth Literacy, and Asthma Outcomes in the Context of a Mobile Health Intervention
Authors: Silverstein Gabriella D. , Styke Sarah C. , Kaur Savneet , Singh Anjani , Green Samuel , Jariwala Sunit P. , Feldman Jonathan
Published: February 2023

Objective

The ASTHMAXcel PRO mobile app provides asthma education and collects asthma outcome data. The objective of this study was to evaluate the associations between health/electronic health literacy (eHealth literacy) and depressive symptoms with app usage and clinical outcomes.

Methods

Adults with persistent asthma were recruited to use the app. Participants completed the Patient Health Questionnaire-9 to assess for depressive symptoms, Asthma Control Test, Mini Asthma Quality of Life (QOL) Questionnaire, and the Newest Vital Sign tool to measure health literacy. Data on a subset of participants were available on eHealth literacy (n = 24) and average number of app logins across 2 months (n = 40).

Results

The total study sample included 96 participants (46% non-Hispanic Black, 44.4% Hispanic). The average participant age was 44.0 (standard deviation = 14.9) years, with 74% identifying as female. Increased depressive symptoms were associated with worse asthma control (β = −0.46, p < .001) and asthma QOL (β = −0.38, p < .001), but not eHealth literacy. Higher eHealth literacy was associated with worse asthma QOL (β = −0.48, p = .02) and more app logins (β = 0.59, p = .04). Newest Vital Sign scores were not associated with any of the other measures.

Conclusions

Depressive symptoms were associated with worse asthma outcomes. eHealth literacy was associated with increased patient engagement with the app and worse asthma QOL, which may reflect patients with worse QOL seeking out health information on the Internet (although directionality could not be assessed). Digital health literacy may be key to increasing patient engagement with mobile health interventions.

Trial Registration: National Clinical Trial No. 03847142, https://clinicaltrials.gov/ct2/show/NCT03847142.
Insulin Resistance and Glycated Hemoglobin in Obesity Are Associated With Preference for Sugar-Sweetened Yogurt: A Pilot Study
Authors: Epstein Leonard H. , Biondolillo Mathew J. , Rizwan Ashfique , Ghanim Husam , Dandona Paresh , Bickel Warren K. , Paluch Rocco A.
Published: February 2023

Objective

Insulin resistance is associated with elevated activation of food reward, which should be associated with an increased reinforcing value of food. Research has also shown that sugar is a macronutrient strongly associated with reward and reinforcing value of food. This research is designed to assess whether insulin resistance is associated with a stronger preference for sugar-sweetened, thus elevating blood glucose responses in obese people with varying degrees of insulin resistance.

Methods

Thirteen people with obesity (body mass index, 39.1 kg/m2; range, 30.0–45.1 kg/m2) with varying degrees of insulin resistance (Homeostatic Model Assessment of Insulin Resistance, 5.2; range, 0.7–11.6) consumed novel flavored-colored yogurts that were sweetened with either sugar or monkfruit daily for 6 days to assess whether when given the choice of sugar-sweetened versus monkfruit-sweetened yogurts to consume, participants preferred sugar-sweetened yogurts.

Results

Participants consumed a greater amount (p = .009) and percentage (p = .04) of sugar-sweetened yogurt earned than monkfruit-sweetened yogurt. The percent of sugar-sweetened versus monkfruit-sweetened yogurt consumed in relationship to amount earned was related to insulin resistance (r = 0.64, p = .019), glycated hemoglobin (r = 0.61, p = .027), insulin (r = 0.58, p = .007), and glucose (r = 0.56, p = .048).

Conclusions

Insulin resistance is associated with preference for sugar-sweetened foods in participants with obesity, which may make it hard to make dietary changes. Research is needed to assess whether treatments that improve insulin resistance also change the preference for sugar-sweetened or high-glycemic-index foods.
Applying a Social Determinants of Health Framework to Guide Digital Innovations that Reduce Disparities in Chronic Disease
Authors: Goldstein Stephanie P. , Tovar Alison , Espel-Huynh Hallie M. , Stowers Kristen Cooksey
Published: February 2023

Chronic diseases are among the top causes of global death, disability, and healthcare expenditure. Digital health interventions (e.g., patient support delivered via technologies such as smartphones, wearables, videoconferencing, social media, virtual reality) may prevent and mitigate chronic disease by facilitating accessible, personalized care. While these tools have promise to reach historically marginalized groups, who are disproportionately affected by chronic disease, evidence suggests digital health interventions could unintentionally exacerbate health inequities. This commentary outlines opportunities to harness recent advancements in technology and research design to drive equitable digital health intervention development and implementation. We apply “calls to action” from the World Health Organization (WHO) Commission on Social Determinants of Health (CSDH) conceptual framework to the development of new, and refinement of existing, digital health interventions that aim to prevent or treat chronic disease by targeting intermediary, social, and/or structural determinants of health. Three mirrored “calls to action” are thus proposed for digital health research: 1) Develop, implement, and evaluate multi-level, context-specific digital health interventions; 2) Engage in intersectoral partnerships to advance digital health equity and social equity more broadly; and 3) Include and empower historically marginalized groups to develop, implement, and access digital health interventions. Using these “action items”, we review several technological and methodological innovations for designing, evaluating, and implementing digital health interventions that have greater potential to reduce health inequities. We also enumerate possible challenges to conducting this work, including leading interdisciplinary collaborations, diversifying the scientific workforce, building trustworthy community relationships, and evolving healthcare and digital infrastructures.
Childhood Social Isolation as a Predictor of Retinal Neuronal Thickness in Middle Age: A Lifecourse Birth Cohort Study
Authors: Barrett-Young Ashleigh , Ambler Antony , Cheyne Kirsten , Guiney Hayley , Kokaua Jesse , Tham Yih Chung , Williams Michael J. A. , Wilson Graham A. , Wong Tien Yin , Poulton Richie
Published: February 2023

Objective

We investigated whether childhood social isolation was associated with retinal neural layer changes in adulthood, and whether this association was independent of other childhood or adulthood risk factors, including adult social isolation.

Methods

Participants were members of the Dunedin Multidisciplinary Health and Development Study, a longitudinal population-based birth cohort from Aotearoa New Zealand (n = 1037), born 1972 to 1973 and followed until age 45 years, with 94% of the living cohort still participating. Social isolation was recorded prospectively at ages 5, 7, 9, and 11 years, from teacher and parent report. Retinal nerve fiber layer (RNFL) and ganglion cell–inner plexiform layer thicknesses were measured via optical coherence tomography at age 45 years.

Results

Childhood social isolation was associated with thinner average RNFL (B = −0.739, p = .02), nasal RNFL (B = −1.118, p = .005), and inferior RNFL (B = −1.524, p = .007), although only nasal RNFL remained significant after adjustment. These associations were not fully explained by other psychosocial or physical health risk factors in childhood or adulthood, nor were they mediated by adult loneliness or social support.

Conclusions

Childhood social isolation was an independent predictor of RNFL thickness in middle age. Highlighting prospective links between childhood psychosocial adversity and retinal neuronal measures will help to inform future research into the utility of retinal neuronal thickness as a biomarker for neurodegeneration.
Malignant Peritoneal Mesothelioma With Butterfly-Shaped Muscle Metastasis
Authors: Li Jian , Yang Jinhui , Hu Shuo
Published: February 2023

Malignant peritoneal mesothelioma is a rare malignancy that may manifest as extraperitoneal metastasis. We describe the findings of 68Ga-FAPI and 18F-FDG PET/CT in a case of malignant peritoneal mesothelioma with widespread muscle metastasis in a butterfly-shaped distribution pattern. We found that FDG and FAPI uptake in the peritoneal tumor and its spread were inhomogeneous. Notably, 68Ga-FAPI PET/CT more clearly showed relevant lesions compared with 18F-FDG PET/CT.
Fluoroquinolone resistance mediated by mutations in gyrA and grlA does not facilitate phage integration in Staphylococcus aureus
Authors: Leinweber Helena , Sieber Raphael N. , Bojer Martin S. , Larsen Jesper , Ingmer Hanne
Published: February 2023

Prophages of the ΦSa3int family are commonly found in human-associated strains of Staphylococcus aureus where they encode factors for evading the human innate immune system. In contrast, they are usually absent in livestock-associated methicillin-resistant S. aureus (LA-MRSA) strains where the phage attachment site is mutated compared to the human strains. However, ΦSa3int phages have been found in a small subset of LA-MRSA strains belonging to clonal complex 398 (CC398), including a lineage that is widespread in pig farms in Northern Jutland, Denmark. This lineage contains amino acid changes in the DNA topoisomerase V and the DNA gyrase encoded by grlA and gyrA, respecively, which have been associated with fluoroquinolone (FQ) resistance. As both of these enzymes are involved in DNA supercoiling, we speculated that the mutations might impact recombination between the ΦSa3int phage and the bacterial chromosome to enhance phage integration. To examine this, we introduced the FQ resistance mutations into S. aureus 8325-4attBLA that carry the mutated CC398-like bacterial attachment site for ΦSa3int phages. Our results failed to reveal significant differences between the FQ-resistant mutant and the wildtype strain with respect to phage integration or phage release. Thus, we conclude that mutations in grlA and gyrA do not contribute to the presence of the ΦSa3int phage in LA-MRSA CC398.
Nasopharyngeal carriage of Streptococcus pneumoniae strains and antimicrobial susceptibility carried by hospitalized pneumonia patients and healthy children under-five years olds in Padang, Indonesia
Authors: Yani Finny Fitry , Julianty Riris Juita , Tafroji Wisnu , Linosefa Linosefa , Ihsan Indra , Masnadi Nice Rachmawati , Safari Dodi
Published: February 2023

Background. Streptococcus pneumoniae is one of the pathogenic bacteria causing invasive pneumococcal diseases (IPD) such as pneumonia, sepsis, meningitis and others, which is commonly reported in children and adult. Streptococcus pneumoniae commonly causes pneumonia in children. However, there is lack of report about the Streptococcus pneumoniae as causative agent of pneumonia in children. Therefore, this study is conducted to describe the serotype distribution and antimicrobial susceptibility profile of S. pneumoniae among children with pneumonia and healthy children.
Material and Methods. We investigated nasopharyngeal carriage rates and serotype distribution of Streptococcus pneumoniae strains and antimicrobial susceptibility carried by hospitalized patients with pneumonia symptom and healthy children under five years olds in Padang, West Sumatra, Indonesia.
Results and Discussion. Out of 131 children, S. pneumoniae strains were carried by 53% and 9,2% of healthy children (35/66) and hospitalized patients (6/65), respectively. Serotype 19F was the most common serotype among the isolated strains (21%) followed by 6C (10%), 14, 34 (7% each), and 1, 23F, 6A, 6B (5% each). Moreover, 55% of the strains (23/42) could be covered by the 13-valent pneumococcal conjugate vaccine. Most of isolates were susceptible to vancomycin (100%), chloramphenicol (93%), clindamycin (76%), erythromycin (71%), and tetracycline (69%).
Conclusion. Serotype 19F was commonly found as multi-drug resistant.
Genomic landscape of virus-associated cancers
Authors: Gomez Karen , Schiavoni Gianluca , Nam Yoonhee , Reynier Jean-Baptiste , Khamnei Cole , Aitken Michael , Palmieri Giuseppe , Cossu Antonio , Levine Arnold , van Noesel Carel , Falini Brunangelo , Pasqualucci Laura , Tiacci Enrico , Rabadan Raul
Published: February 2023

It has been estimated that 15%-20% of human cancers are attributable to infections, mostly by carcinogenic viruses. The incidence varies worldwide, with a majority affecting developing countries. Here, we present a comparative analysis of virus-positive and virus-negative tumors in nine cancers linked to five viruses. We find that virus-positive tumors occur more frequently in males and show geographical disparities in incidence. Genomic analysis of 1,658 tumors reveals virus-positive tumors exhibit distinct mutation signatures and driver gene mutations and possess a lower somatic mutation burden compared to virus-negative tumors of the same cancer type. For example, compared to the respective virus-negative counterparts, virus-positive cases across different cancer histologies had less often mutations ofTP53and deletions of 9p21.3/CDKN2A-CDKN1A; Epstein-Barr virus-positive (EBV+) gastric cancer had more frequent mutations ofEIF4A1andARID1Aand less marked mismatch repair deficiency signatures; and EBV-positive cHL had fewer somatic genetic lesions of JAK-STAT, NF-κB, PI3K-AKT and HLA-I genes and a less pronounced activity of the aberrant somatic hypermutation signature. In cHL, we also identify germline homozygosity in HLA class I as a potential risk factor for the development of EBV-positive Hodgkin lymphoma. Finally, an analysis of clinical trials of PD-(L)1 inhibitors in four virus-associated cancers suggested an association of viral infection with higher response rate in patients receiving such treatments, which was particularly evident in gastric cancer and head and neck squamous cell carcinoma. These results illustrate the epidemiological, genetic, prognostic, and therapeutic trends across virus-associated malignancies.
Vaccine waning and immune escape drive the second surge of Omicron spread in Hong Kong: A modeling study
Authors: Zou Yuling , Lo Wing-Cheong , Ming Wai-Kit , Yuan Hsiang-Yu
Published: February 2023

The Omicron subvariant BA.2 caused the start of the fifth epidemic wave in Hong Kong in early 2022, leading to a significant outbreak and triggering more people get immunized in a population with relatively low vaccine coverage. About half a year later, a second outbreak, largely dominated by BA.4 and BA.5 subvariants, began to spread, which peaked within few months. How the waning of the vaccine protection and the immune escape properties together with other factors, including social distancing and outdoor temperature, drove the second surge of infections is unknown. The challenge is that basic epidemic modeling is not able to capture longitudinal change in vaccine waning and dose interval. We developed mathematical equations to formulate continuous change of vaccine waning after observing empirical serological data and incorporate them into a multi-strain discrete-time SEIR (Susceptible-Exposed-Infectious-Removed) model. Using the reported cases during the first outbreak as the training set together with daily vaccination rates, population mobility and temperature, the model successfully predicted the second surge and the replacement by BA.4/5, leading to a cumulative number of cases about 543,600 (7.27% of total population). If vaccine protection maintained without decreasing, the number of predicted cumulative cases reduced 35%. If perfect vaccine coverage reached (100%) by 1stJune, the number of cases was only partially reduced 18.65%. Moderate level of social distancing (10% reduction in population mobility) reduced only 13.78% cases, which was not able to prevent the second surge. The results suggest future local outbreaks will remain as long as new immune escape happens with waning immunity, even if the moderate level of social distancing is present. Therefore, a more accurate model forecasting considering waning immunity remains needed in order to allow a better preparation of the next outbreaks.
Bevacizumab in ovarian cancer: time-dependent changes in risk of progression
Authors: Takamatsu Shiro , Nakai Hidekatsu , Yamaguchi Ken , Hamanishi Junzo , Mandai Masaki , Matsumura Noriomi
Published: February 2023

Background

Bevacizumab has been used in the first-line and recurrent treatment of ovarian cancer. However, the time-dependent changes in the effects of bevacizumab administration are not fully understood.

Methods

The ICON7-A cohort was generated from two ancillary analyses of the ICON7 trial. ICON7-A tumors were classified as homologous recombination deficient (HRD) or non-HRD based on their gene expression profiles. Kaplan-Meier curves from published phase III trials were graphically analyzed to examine changes in the risk of progression over time between groups.

Results

In the ICON7-A cohort, the risk of progression in the bevacizumab group (Bev+) compared to the control group (Bev-) was lowest at 6 months. Thereafter, the risk in Bev+ gradually increased and became higher than in Bev-after discontinuation of bevacizumab at 12 months, showing a “rebound effect”. Restricted mean survival analysis showed that Bev+ had significantly better progression-free survival (PFS) than Bev-before bevacizumab discontinuation, but had significantly worse PFS after bevacizumab discontinuation. The rebound effect was observed both in HRD and non-HRD tumors of the serous subtype, but not in the non-serous subtype. In Kaplan-Meier curve image-based analysis, time-dependent changes in the risk of progression, including rebound effects, were replicated in the overall ICON7 and GOG-0218 cohorts and in their subgroups stratified by prognostic factors, presence of HR-associated mutations and chemotherapy sensitivity. In contrast, no rebound effect was observed in the studies GOG-0213, OCEANS, AURERIA and MITO16B, in which relapsed patients received bevacizumab until progression.

Conclusion

In ovarian cancer, bevacizumab reduces progression for approximately one year after initiation, but discontinuation may increase subsequent progression in the serous subtype regardless of HRD status. The results suggest that in the first-line treatment of ovarian cancer, bevacizumab is more beneficial in patients with a short expected survival who are unlikely to be affected by the rebound effect.
Service Availability and Readiness for Basic Emergency Obstetric and Newborn Care: Analysis from Nepal Health Facility Survey 2021
Authors: Pandey Achyut Raj , Adhikari Bikram , Lamichhane Bipul , Joshi Deepak , Regmi Shophika , Lal Bibek Kumar , Dahal Sagar , Baral Sushil Chandra
Published: February 2023

Background

Although there has been significant improvement in maternal and newborn health, Nepal needs further acceleration in improving access to and coverage of services to achieve Sustainable Development Goals by 2030. In this context, we aimed to analyze availability and readiness for Basic Emergency Obstetric and Neonatal Care (BEmONC) services in Nepal using data from Nepal Health Facility Survey (NHFS), 2021.

Methods

We analyzed nationally representative NHFS, 2021 data to determine availability and readiness of HFs for BEmONC services based on the “Service Availability and Readiness” manual of World Health Organizations. We performed weighted descriptive and inferential analysis to account complex survey design of NHFS 2021. We summarized continuous variables with mean, standard deviation, median and interquartile range whereas categorical variables with percent and 95% confidence interval (CI). We applied simple, and multiple linear regression to determine factors associated with readiness of HFs for BEmONC services.

Results

The proportion of facilities with all BEmONC signal function available was 2.49% at the national level with Madhesh having the highest (5.22%) while Gandaki having the lowest (1.22%) availability. BEmONC service availability was relatively lower in rural setting and peripheral facilities. The overall readiness score for BEmONC services is 54.14, with domains of guidelines/staff, equipment/supplies, and medicines/commodities having scores of 21.16, 76.76, and 64.50 respectively. In multivariable analysis, level of facilities, province, urban rural setting, ecological belt, presence of external supervision, 24-hour duty schedule and number of beds were found to have statistically significant association with BEmONC service readiness.

Conclusion

The readiness of HFs for BEmONC services in Nepal is relatively poor and can be improved by increasing service provision, expanding service hours to 24-hours a day, increasing availability of essential medicines and equipment, enhanced monitoring, and conducting periodic review of maternal and newborn deaths at HFs.
Whole-brain structural connectome asymmetry in autism
Authors: Yoo Seulki , Jang Yurim , Hong Seok-Jun , Park Hyunjin , Valk Sofie L. , Bernhardt Boris C. , Park Bo-yong
Published: February 2023

Abstract

Autism spectrum disorder is a common neurodevelopmental condition that manifests as a disruption in sensory and social skills. Although it has been shown that the brain morphology of individuals with autism is asymmetric, how this differentially affects the structural connectome organization of each hemisphere remains under-investigated. We studied whole-brain structural connectivity-based brain asymmetry in 47 individuals with autism and 37 healthy controls using diffusion magnetic resonance imaging obtained from the Autism Brain Imaging Data Exchange initiative. By leveraging dimensionality reduction techniques, we constructed low-dimensional representations of structural connectivity and calculated their asymmetry index. We compared the asymmetry index between individuals with autism and neurotypical controls and found atypical structural connectome asymmetry in the sensory, default-mode, and limbic networks and the caudate in autism. Network communication provided topological underpinnings by demonstrating that the temporal and dorsolateral prefrontal regions showed reduced global network communication efficiency and decreased send-receive network navigation in the caudate region in individuals with autism. Finally, supervised machine learning revealed that structural connectome asymmetry is associated with communication-related autistic symptoms and nonverbal intelligence. Our findings provide insights into macroscale structural connectome alterations in autism and their topological underpinnings.
Estimates of protection against SARS-CoV-2 infection and severe COVID-19 in Germany before the 2022/2023 winter season - the IMMUNEBRIDGE project
Authors: Lange Berit , Jaeger Veronika K , Harries Manuela , Rücker Viktoria , Streeck Hendrik , Blaschke Sabine , Petersmann Astrid , Toepfner Nicole , Nauck Matthias , Hassenstein Max J , Dreier Maren , Von Holt Isabell , Budde Axel , Bartz Antonia , Ortmann Julia , Kurosinski Marc-André , Berner Reinhard , Borsche Max , Brandhorst Gunnar , Brinkmann Melanie , Budde Kathrin , Deckena Marek , Engels Geraldine , Fenzlaff Marc , Härtel Christoph , Hovardovska Olga , Katalinic Alexander , Kehl Katja , Kohls Mirjam , Krüger Stefan , Lieb Wolfgang , Meyer-Schlinkmann Kristin M , Pischon Tobias , Rosenkranz Daniel , Rübsamen Nicole , Rupp Jan , Schäfer Christian , Schattschneider Mario , Schlegtendal Anne , Schlinkert Simon , Schmidbauer Lena , Schulze-Wundling Kai , Störk Stefan , Tiemann Carsten , Völzke Henry , Winter Theresa , Klein Christine , Liese Johannes , Brinkmann Folke , Ottensmeyer Patrick F , Reese Jens-Peter , Heuschmann Peter , Karch André
Published: February 2023

Despite the need to generate valid and reliable estimates of protection against SARS-CoV-2 infection and severe course of COVID-19 for the German population in summer 2022, there was a lack of systematically collected population-based data allowing for the assessment of the protection level in real-time.

In the IMMUNEBRIDGE project, we harmonised data and biosamples for nine population-/hospital-based studies (total number of participants n=33,637) to provide estimates for protection levels against SARS-CoV-2 infection and severe COVID-19 between June and November 2022. Based on evidence synthesis, we formed a combined endpoint of protection levels based on the number of self-reported infections/vaccinations in combination with nucleocapsid/spike antibody responses (“confirmed exposures”). Four confirmed exposures represented the highest protection level, and no exposure represented the lowest.

Most participants were seropositive against the spike antigen; 37% of the participants ≥79 years had less than four confirmed exposures (highest level of protection) and 5% less than three. In the subgroup of participants with comorbidities, 46-56% had less than four confirmed exposures. We found major heterogeneity across federal states, with 4%-28% of participants having less than three confirmed exposures.

Using serological analyses, literature synthesis and infection dynamics during the survey period, we observed moderate to high levels of protection against severe COVID-19, whereas the protection against SARS-CoV-2 infection was low across all age groups. We found relevant protection gaps in the oldest age group and amongst individuals with comorbidities, indicating a need for additional protective measures in these groups.
Social Determinants of Health Data Quality at Different Levels of Geographic Detail
Authors: Greer Melody L. , Garza Maryam Y. , Sample Steve , Bhattacharyya Sudeepa
Published: February 2023

Social determinants of health (SDOH) impact 80% of health outcomes from acute to chronic disorders, and attempts are underway to provide these data elements to clinicians. It is, however, difficult to collect SDOH data through (1) surveys, which provide inconsistent and incomplete data, or (2) aggregates at the neighborhood level. Data from these sources is not sufficiently accurate, complete, and up-to-date. To demonstrate this, we have compared the Area Deprivation Index (ADI) to purchased commercial consumer data at the individual-household level. The ADI is composed of income, education, employment, and housing quality information. Although this index does a good job of representing populations, it is not adequate to describe individuals, especially in a healthcare context. Aggregate measures are, by definition, not sufficiently granular to describe each individual within the population they represent and may result in biased or imprecise data when simply assigned to the individual. Moreover, this problem is generalizable to any community-level element, not just ADI, in so far as they are an aggregate of the individual community members.
An integrated transcriptomics–functional genomics approach reveals a small RNA that modulatesBacteroides thetaiotaomicronsensitivity to tetracyclines
Authors: Ryan Daniel , Bornet Elise , Prezza Gianluca , Alampalli Shuba Varshini , Carvalho Taís Franco de , Felchle Hannah , Ebbecke Titus , Hayward Regan , Deutschbauer Adam M. , Barquist Lars , Westermann Alexander J.
Published: February 2023

Gene expression plasticity allows bacteria to adapt to diverse environments, tie their metabolism to available nutrients, and cope with stress. This is particularly relevant in a niche as dynamic and hostile as the human intestinal tract, yet transcriptional networks remain largely unknown in gutBacteroidesspp. Here, we map transcriptional units and profile their expression levels inBacteroides thetaiotaomicronover a suite of 15 defined experimental conditions that are relevantin vivo, such as variation of temperature, pH, and oxygen tension, exposure to antibiotic stress, and growth on simple carbohydrates or on host mucin-derived glycans. Thereby, we infer stress- and carbon source-specific transcriptional regulons, including conditional expression of capsular polysaccharides and polysaccharide utilization loci, and expand the annotation of small regulatory RNAs (sRNAs) in this organism. Integrating this comprehensive expression atlas with transposon mutant fitness data, we identify conditionally important sRNAs. One example is MasB, whose inactivation led to increased bacterial tolerance of tetracyclines. Using MS2 affinity purification coupled with RNA sequencing, we predict targets of this sRNA and discuss their potential role in the context of the MasB-associated phenotype. Together, this transcriptomic compendium in combination with functional sRNA genomics—publicly available through a new iteration of the ‘Theta-Base’ web browser (www.helmholtz-hiri.de/en/datasets/bacteroides-v2)—constitutes a valuable resource for the microbiome and sRNA research communities alike.
Ultrahigh-affinity transport proteins from ubiquitous marine bacteria reveal mechanisms and global patterns of nutrient uptake
Authors: Clifton Ben E. , Alcolombri Uria , Jackson Colin J. , Laurino Paola
Published: February 2023

SAR11 bacteria are the most abundant members of the global ocean microbiome and have a broad impact on ocean ecosystems. To thrive in their competitive oligotrophic environments, these bacteria rely on solute-binding proteins (SBPs) that facilitate nutrient uptake through ABC transporters. Nonetheless, previous studies have been unable to access the molecular mechanisms and functions of these transporters because they rely heavily on homology-based predictions. These mechanisms and functions are essential to understand biogeochemical cycling in the ocean, including assimilation of dissolved organic matter (DOM). Here, by doing a biochemical study of the collective behavior of all SBPs in a SAR11 bacterium, we discover that these transporters have unprecedented binding affinity (Kd≥30 pM) and unexpectedly high binding specificity, revealing molecular mechanisms for oligotrophic adaptation. Our study uncovers new carbon sources for the SAR11 bacteria and provides an accurate biogeographical map of nutrient uptake in the ocean. Our results show how functional adaptation at the molecular level in ubiquitous marine bacteria impacts global patterns of DOM assimilation and provides insight into the contribution of different compounds to oceanic nutrient cycles.
Assessment of the acute effects of 2C-B vs psilocybin on subjective experience, mood and cognition
Authors: Mallaroni Pablo , Mason Natasha L. , Reckweg Johannes T. , Paci Riccardo , Ritscher Sabrina , Toennes Stefan W. , Theunissen Eef L. , Kuypers Kim P.C. , Ramaekers Johannes G.
Published: February 2023

2,5-dimethoxy-4-bromophenethylamine (2C-B) is a hallucinogenic phenethylamine derived from mescaline. Observational and preclinical data have suggested it to be capable of producing both subjective and emotional effects on par with other classical psychedelics and entactogens. Whereas it is the most prevalently used novel serotonergic hallucinogen to date, it’s acute effects and distinctions from classical progenitors have yet to be characterised in a controlled study. We assessed for the first time the immediate acute subjective, cognitive, and cardiovascular effects of 2C-B (20 mg) in comparison to psilocybin (15mg) and placebo in a within-subjects, double-blind, placebo-controlled study of 22 healthy psychedelic-experienced participants. 2C-B elicited alterations of waking consciousness of a psychedelic nature, with dysphoria, subjective impairment, auditory alterations, and affective elements of ego dissolution largest under psilocybin. Participants demonstrated equivalent psychomotor slowing and spatial memory impairments under either compound compared to placebo, as indexed by the Digit Symbol Substitution Test (DSST), Tower of London (TOL) and Spatial Memory Task (SMT). Neither compound produced empathogenic effects on the Multifaceted Empathy Test (MET). 2C-B induced transient pressor effects to a similar degree as psilocybin. The duration of self-reported effects of 2C-B was shorter than that of psilocybin, largely resolving within 6 hours. Present findings support the categorisation of 2C-B as a subjectively “lighter” psychedelic. Tailored dose-effect studies are needed to discern the pharmacokinetic dependency of 2C-B’s experiential overlaps.
Filament formation drives catalysis by glutaminase enzymes important in cancer progression
Authors: Feng Shi , Aplin Cody , Nguyen Thuy-Tien T. , Milano Shawn K. , Cerione Richard A.
Published: February 2023

The glutaminase enzymes GAC and GLS2 catalyze the hydrolysis of glutamine to glutamate, satisfying the ‘glutamine addiction’ of cancer cells. They are the targets of anti-cancer drugs; however, their mechanisms of activation and catalytic activity have been unclear. Here we demonstrate that the ability of GAC and GLS2 to form filaments is directly coupled to their catalytic activity and present their cryo-EM structures which provide an unprecedented view of the conformational states essential for catalysis. Filament formation guides an ‘activation loop’ to assume a specific conformation that works together with a ‘lid’ to close over the active site and position glutamine for nucleophilic attack by an essential serine. Our findings highlight how ankyrin repeats on GLS2 regulate enzymatic activity, while allosteric activators stabilize, and clinically relevant inhibitors block, filament formation that enables glutaminases to catalyze glutaminolysis and support cancer progression.
Allergic Asthma Responses Are Dependent on Macrophage Ontogeny
Authors: Tighe Robert M. , Birukova Anastasiya , Malakhau Yuryi , Kobayashi Yoshihiko , Vose Aaron T. , Chandramohan Vidya , Cyphert-Daly Jaime M. , Cumming R. Ian , Kirshner Helene Fradin , Tata Purushothama R. , Ingram Jennifer L. , Gunn Michael D. , Que Loretta G. , Yu Yen-Rei A.
Published: February 2023

The ontogenetic composition of tissue-resident macrophages following injury, environmental exposure, or experimental depletion can be altered upon re-establishment of homeostasis. However, the impact of altered resident macrophage ontogenetic milieu on subsequent immune responses is poorly understood. Hence, we assessed the effect of macrophage ontogeny alteration following return to homeostasis on subsequent allergic airway responses to house dust mites (HDM). Using lineage tracing, we confirmed alveolar and interstitial macrophage ontogeny and their replacement by bone marrow-derived macrophages following LPS exposure. This alteration in macrophage ontogenetic milieu reduced allergic airway responses to HDM challenge. In addition, we defined a distinct population of resident-derived interstitial macrophages expressing allergic airway disease genes, located adjacent to terminal bronchi, and reduced by prior LPS exposure. These findings support that the ontogenetic milieu of pulmonary macrophages is a central factor in allergic airway responses and has implications for how prior environmental exposures impact subsequent immune responses and the development of allergy.
Functional diversity and soil nutrients regulate the interannual variability in gross primary productivity
Authors: Yan Pu , Zhang Jiahui , He Nianpeng , Zhang Weikang , Liu CongCong , Fernández‐Martínez Marcos
Published: February 2023

Global change, encompassing rising temperatures and an increase in extreme precipitation events, has influenced vegetation photosynthesis; this can be seen in the gross primary productivity (GPP) of terrestrial ecosystems, which, over time affects the global carbon cycle. The impact of climate on interannual variability in GPP (GPPIAV) has been extensively explored in the literature. Other changing factors driven by global change, such as biodiversity and soil nutrient availability, are vital in predicting the future of the biosphere. However, the roles of these factors remain unclear.

We combined (i) data from 454 community plots collected using standard protocols from 2013 to 2019 across China, (ii) plant trait data and phylogenetic information of more than 2500 plant species, and (iii) soil nutrient data that we measured. Using these data from 72 “real‐world” ecosystems located across a range of environmental conditions and species pools, we investigated the role of environmental factors including temperature, precipitation and soil nutrients and multifaceted diversity (i.e. species richness, hypervolume‐based functional diversity, and phylogenetic diversity) in mediating the magnitude of GPPIAV using multi‐model averaging and structural equation modelling.

We found that soil nutrients and functional diversity are the main determinants of the magnitude of GPPIAV and that climate effects are predominantly mediated by multifaceted diversity.

Synthesis. We provide strong evidence that ecosystems with higher biodiversity have less variable annual biomass production and decrease the extent of GPPIAV through compensatory effects across diverse ecosystems. Nutrient‐rich ecosystems are likely to buffer the impact of climate variability on ecosystem carbon uptake better than nutrient‐poor ecosystems. Our results demonstrate that biodiversity plays a crucial role in buffering the effects of environmental variability on carbon uptake in terrestrial ecosystems.
Quantifying plant biomass and seed production in camelina (Camelina sativa (L.) Crantz) across a large range of plant densities: Modelling approaches
Authors: Bakhshandeh Esmaeil , Hosseini Sanehkoori Fatemeh , Ghorbani Hamidreza , Nematzadeh Ghorban Ali , Sekrafi Mansour , Abdellaoui Raoudha , Yaghoubi Khanghahi Mohammad , Crecchio Carmine
Published: February 2023

To date, there has been little agreement on supporting the hypothesis that how some key vegetative traits of camelina (Camelina sativa (L.) Crantz var. ‘Soheil’) are dependent on plant biomass. Therefore, the main aim of this investigation was to quantify the relationship between the size of camelina plants and seed production across a broad‐range of plant densities through modelling approaches. To make a wide range of plant densities, a fan design was used in eight replicates in an experimental field at Sari Agricultural Sciences and Natural Resources University, Iran. To quantify the relation between plant density and other plant traits, a regression analysis was carried out and the coefficient of determination (R2) was considered to evaluate the goodness of fit model. A power model (y = axb) could describe well the relationship between plant density (ranged 113–2905 plants m−2) and plant biomass, seed production, number of seeds per plant, stem diameter, and siliques number, with the coefficient of determination (R2) values of 0.85, 0.87, 0.65, 0.64, and 0.90, respectively. The harvest indexes were 13.8%–26.9%, depending on plant density. Seed production per plant was positively correlated to the siliques number (r = 0.85), the branch number (r = 0.80), and the seed number (r = 0.99) which could be key components of camelina seed production per plant. Furthermore, no significant correlation was found among plant height, thousand‐seed weight, and harvest index with seed production per plant. In conclusion, plant biomass could be considered an important trait to predict plant growth models of camelina. Also, a lower plant density of camelina can be compensated by a greater number of siliques, branches and seeds per plant.
Age‐related changes to adipose tissue and peripheral neuropathy in genetically diverse HET3 mice differ by sex and are not mitigated by rapamycin longevity treatment
Authors: Willows Jake W. , Robinson Morganne , Alshahal Zahra , Morrison Samantha K. , Mishra Gargi , Cyr Harrison , Blaszkiewicz Magdalena , Gunsch Gilian , DiPietro Sabrina , Paradie Emma , Tero Benjamin , Harrington Anne , Ryzhova Larisa , Liaw Lucy , Reifsnyder Peter C. , Harrison David E. , Townsend Kristy L.
Published: February 2023

Neural communication between the brain and adipose tissues regulates energy expenditure and metabolism through modulation of adipose tissue functions. We have recently demonstrated that under pathophysiological conditions (obesity, diabetes, and aging), total subcutaneous white adipose tissue (scWAT) innervation is decreased (‘adipose neuropathy’). With advanced age in the C57BL/6J mouse, small fiber peripheral nerve endings in adipose tissue die back, resulting in reduced contact with adipose‐resident blood vessels and other cells. This vascular neuropathy and parenchymal neuropathy together likely pose a physiological challenge for tissue function. In the current work, we used the genetically diverse HET3 mouse model to investigate the incidence of peripheral neuropathy and adipose tissue dysregulation across several ages in both male and female mice. We also investigated the anti‐aging treatment rapamycin, an mTOR inhibitor, as a means to prevent or reduce adipose neuropathy. We found that HET3 mice displayed a reduced neuropathy phenotype compared to inbred C56BL/6 J mice, indicating genetic contributions to this aging phenotype. Compared to female HET3 mice, male HET3 mice had worse neuropathic phenotypes by 62 weeks of age. Female HET3 mice appeared to have increased protection from neuropathy until advanced age (126 weeks), after reproductive senescence. We found that rapamycin overall had little impact on neuropathy measures, and actually worsened adipose tissue inflammation and fibrosis. Despite its success as a longevity treatment in mice, higher doses and longer delivery paradigms for rapamycin may lead to a disconnect between life span and beneficial health outcomes.