bluuebunny/crossref_metadata_2025 huggingface dataset:
POEMS syndrome characterized by bone lesions: A case report
Authors: Wang Yang , Liu Yalong , Huang Xiaoli , Peng Lan , Zhang Zhijun
Published: December 2023

Rationale:

POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal paraproteinemia, and skin changes) syndrome is a rare clinical syndrome characterized by multiple peripheral neuropathies, hepatosplenomegaly, endocrine disorders, monoclonal paraproteinemia, and dermatosis. The main manifestations of POMES were nerve and skin changes, and bone disease was not reported. Here, we report a case of POEMS syndrome with the main manifestation of bone lesions.

Patient concerns:

POMES is rare and its clinical manifestations are complex, making it difficult for patients to find the department they should visit. It is easy to miss diagnosis and misdiagnosis, delay the treatment time of patients, and affect the prognosis.

Diagnosis interventions:

The patient was admitted to the gastroenterology department due to hepatic insufficiency. Multiple osteogenic changes were found by improved enhanced CT due to screening for causes of hepatic insufficiency, and spleen enlargement was indicated by abdominal ultrasound. Due to the involvement of multiple system problems, and follow-up of medical history, it was found that there was a history of discoloration of the distal limb in cold weather in the past 5 years. All things considered, it may be POMES. Further refinement of the bone marrow examination revealed active proliferation of granulocytes and erythrocytes. Bone marrow biopsy showed active hyperplasia, dominated by granulocytes. IFE showed IgA (type λ) and monoclonal myeloma (M) protein bands. To sum up, POMES diagnosis is considered.

Outcomes:

After the diagnosis is clear and the informed consent of the patient and his family is obtained, prednisone acetate is anti-inflammatory, lenalidomide is used to regulate immune function, liver and stomach protection treatment and bile secretion promotion are given. The patient reported improvement in liver function, significant improvement in overall and limb stiffness, and was discharged with improvement.

Lessons:

Although bone lesions are not typically the main manifestation of POEMS syndrome, this diagnosis should be considered when this manifestation is combined with organ enlargement, skin changes, and peripheral neuropathy. In addition, the collection of medical history is crucial, when there is a clinical manifestation and auxiliary examination does not match, the idea should be expanded according to the relevant evidence, and finally make the corresponding diagnosis.
Hypersensitivity reaction to nedaplatin: A case report and literature review
Authors: Gan Kelun , Ma Daiyuan
Published: December 2023

Rationale:

Although rare, systemic hypersensitivity reactions to nedaplatin chemotherapy arise rapidly and can be life-threatening. The causes are unclear, and multiple potential mechanisms exist. Here, we report a case of systemic hypersensitivity reaction to nedaplatin and review the literature to establish a recommended protocol.

Patient concerns:

A 62-year-old man was being treated for squamous lung cancer with multiple metastases. On the first day of chemotherapy, 5 minutes after nedaplatin infusion, he developed panic, shortness of breath, and dyspnea with rapid heart rate, reduced oxygen saturation, and elevated blood pressure.

Diagnoses:

The symptoms indicated that the patient had developed a severe hypersensitivity reaction to nedaplatin, which could be life-threatening without immediate intervention.

Intervention:

Nedaplatin was discontinued, and he was treated with oxygen, ECG monitoring, finger pulse oximeter monitoring, 10 mg dexamethasone sodium phosphate injected intravenously, 20 mg diphenhydramine hydrochloride injected intramuscularly, and 40 mg methylprednisolone sodium succinate injected intravenously.

Outcome:

His allergic symptoms resolved, and once his vital signs stabilized, he was given 5 mg oral desloratadine once daily and 10 mg oral ebastine once daily to alleviate the effects of the allergic reaction. Once his vital signs remained stable without any special supportive treatment, he was discharged from the hospital. His chemotherapy regimen was discontinued, with no plan for a follow-up treatment due to the possibility of cross-allergic reactions between platinum-based drugs.

Lessons:

Clinical use of nedaplatin should be monitored and managed intensively for prevention and treatment of hypersensitivity reactions. Care should be taken to control the titration rate during infusion while closely monitoring vital signs. Clinical staff should be prepared to treat allergic symptoms as soon as they appear. The acute phase should involve immediate discontinuation of the drug; intravenous saline infusion for volume expansion; rapid assessment of circulation, airway, respiration, state of consciousness, and skin condition; and administration of oxygen, antihistamines, and epinephrine as appropriate for anaphylaxis. More randomized clinical trials are needed to elucidate appropriate preventative and management strategies to improve patient safety and support their successful completion of clinical treatment programs.
Comparison of on-scene Glasgow Coma Scale with GCS-motor for prediction of 30-day mortality and functional outcomes of patients with trauma in Asia
Authors: Chien Yu-Chun , Chiang Wen-Chu , Chen Chi-Hsin , Sun Jen-Tang , Jamaluddin Sabariah Faizah , Tanaka Hideharu , Ma Matthew Huei-Ming , Huang Edward Pei-Chuan , Lin Mau-Roung ,   The PATOS Clinical Research Network
Published: December 2023

Background and importance

This study compared the on-scene Glasgow Coma Scale (GCS) and the GCS-motor (GCS-M) for predictive accuracy of mortality and severe disability using a large, multicenter population of trauma patients in Asian countries.

Objective

To compare the ability of the prehospital GCS and GCS-M to predict 30-day mortality and severe disability in trauma patients.

Design

We used the Pan-Asia Trauma Outcomes Study registry to enroll all trauma patients >18 years of age who presented to hospitals via emergency medical services from 1 January 2016 to November 30, 2018.

Settings and participants

A total of 16,218 patients were included in the analysis of 30-day mortality and 11 653 patients in the analysis of functional outcomes.

Outcome measures and analysis

The primary outcome was 30-day mortality after injury, and the secondary outcome was severe disability at discharge defined as a Modified Rankin Scale (MRS) score ≥4. Areas under the receiver operating characteristic curve (AUROCs) were compared between GCS and GCS-M for these outcomes. Patients with and without traumatic brain injury (TBI) were analyzed separately. The predictive discrimination ability of logistic regression models for outcomes (30-day mortality and MRS) between GCS and GCS-M is illustrated using AUROCs.

Main results

The primary outcome for 30-day mortality was 1.04% and the AUROCs and 95% confidence intervals for prediction were GCS: 0.917 (0.887–0.946) vs. GCS-M:0.907 (0.875–0.938), P = 0.155. The secondary outcome for poor functional outcome (MRS ≥ 4) was 12.4% and the AUROCs and 95% confidence intervals for prediction were GCS: 0.617 (0.597–0.637) vs. GCS-M: 0.613 (0.593–0.633), P = 0.616. The subgroup analyses of patients with and without TBI demonstrated consistent discrimination ability between the GCS and GCS-M. The AUROC values of the GCS vs. GCS-M models for 30-day mortality and poor functional outcome were 0.92 (0.821–1.0) vs. 0.92 (0.824–1.0) (P = 0.64) and 0.75 (0.72–0.78) vs. 0.74 (0.717–0.758) (P = 0.21), respectively.

Conclusion

In the prehospital setting, on-scene GCS-M was comparable to GCS in predicting 30-day mortality and poor functional outcomes among patients with trauma, whether or not there was a TBI.
Successful Crizotinib-targeted Therapy of Pediatric Unresectable ERC1::ALK Fusion Sarcoma
Authors: Wood Megan L. , Fanburg-Smith Julie C. , Brian James M. , White Jason C. , Powell Jonathan L. , Freiberg Andrew S.
Published: December 2023

Anaplastic lymphoma kinase (ALK)-fusion sarcomas are rare part of the emerging theoretically targetable tyrosine kinase RAS::MAPK pathway fusion myopericytic-ovoid sarcomas. We report our clinicopathologic and treatment experience with an ALK fusion sarcoma. A novel ELKS/RAB6-interacting/CAST family member 1–unaligned ALK fusion infiltrative nonmetastatic low-grade sarcoma of the right hand of a 15-month-old male was treated with crizotinib, an ALK tyrosine kinase inhibitor as oral monotherapy, inducing complete radiographic and clinical resolution by 10 months and sustained response now over 12 months after elective discontinuation. Crizotinib can successfully be used to treat unresectable novel ALK fusion sarcomas.
Rare case in Somalia: Fahr’s syndrome
Authors: Adam Aisha M. , Sheikh Omar A. , Roble Miski A. , Yaşar Mehmet Z. , Mohamed Shukri S. , Kassim Mohamed M.
Published: December 2023

Introduction and importance:

Fahr’s syndrome is primarily familial, autosomal dominant, and genetically diverse. Basal ganglia calcification that is bilaterally symmetrical is a hallmark of this illness. Although the specific origins of this illness are unknown, it may be brought on by problems with calcium metabolism, infections, toxins, hereditary factors, hypoparathyroidism, and pseudohypoparathyroidism. The prevalence of this syndrome is less than 0.5%.

Case presentation:

An 11-year-old female comes to the Emergency Department with her parents complaining of high-grade fever and convulsions for 1 week. Convulsion, which is a generalized tonic–clonic seizure, duration was ~5 min and associated with urinary incontinence and biting tongue. On examination, the patient was confused and irritable. Vital signs were normal; there is weakness in the right arm and right leg, associated with irregular movement. There was alternation in her level of consciousness, slurring of speech, and psychiatric symptoms. Another aspect of the neurological examination and systems was normal, and there was no meningeal irritation.

Clinical discussion:

The pathogenesis of Fahr’s syndrome is not completely known. The calcification is caused by flaws in the transport of radioactive particles and tissue damage caused by free radicals. Bilateral calcification found on a computed tomography (CT) scan of the brain, autosomal dominant inheritance, the absence of any infection, drugs, or toxins, the absence of mitochondrial dysfunction, and the presence of progressive neurological dysfunction is the clinical criteria for diagnosing Fahr’s syndrome.

Conclusion:

Basal ganglia calcification that is bilaterally symmetrical is a hallmark of Fahr’s syndrome. CT scans are the gold standard for conclusively diagnosing Fahr’s syndrome.
Cumulative Effects of Comorbid Burden and Overactive Bladder Symptoms on Fall Risk Among Older Women Seeking Treatment for Urogynecologic Conditions
Authors: Fisher Steve R. , Halder Gabriela E. , Lee Mi Jung , Allen Lindsay , Kilic Gokhan S.
Published: December 2023

(Abstracted from Urogynecology 2023;29:763–769)

Beyond impaired quality of life, the effects of urinary incontinence (UI) and overactive bladder (OAB) put older adults with this condition as at risk of social isolation, institutionalization, loss of independence, and injurious falls. Although the prevalence of older women with these conditions is reported as more than 30%, it is also believed that fewer than half of affected persons report bladder control problems to their health care providers.
Atypical Postmortem “Incaprettamento” After an Honor Homicide
Authors: Porzio Antonietta , Feola Alessandro , La Sala Francesco , Pietra Bruno Della , Campobasso Carlo Pietro
Published: December 2023

Honor killing is a murder carried out to protect the family's reputation by actions that are perceived as shameful. Usually, honor killing occurs to preserve family's honor, which has been violated by adulteries, premarital pregnancies, or inappropriate relationships. In Southern Italy, the culture of honor is quite strong especially among the local criminal organizations. Honor crimes by Italian Mafia are intended to have an admonitory significance, and they can be carried out following a macabre ritual of “incaprettamento.” The aim is to humiliate the victim treating him like an animal, a bonded young goat where the victim is secured by a rope passing behind the back from the upper to lower extremities. In this case study, the honor homicide was perpetrated against the lover of a butcher's wife by sharp weapon, followed by a postmortem atypical incaprettamento of the corpse. The wrists and ankles were tied together by ropes, and the extremities were fixed to the abdomen with a string. The body was also wrapped in a plastic tape after penile amputation. According to killer's confession, the mutilation and the incaprettamento were expressions of revenge and contempt for the victim to restore the honor lost.
Constructing bilayer and volumetric atrial models at scale
Authors: Roney Caroline H. , Solis Lemus Jose Alonso , Lopez Barrera Carlos , Zolotarev Alexander , Ulgen Onur , Kerfoot Eric , Bevis Laura , Misghina Semhar , Vidal Horrach Caterina , Jaffery Ovais A. , Ehnesh Mahmoud , Rodero Cristobal , Dharmaprani Dhani , Ríos-Muñoz Gonzalo R. , Ganesan Anand , Good Wilson W. , Neic Aurel , Plank Gernot , Hopman Luuk H. G. A. , Götte Marco J. W. , Honarbakhsh Shohreh , Narayan Sanjiv M. , Vigmond Edward , Niederer Steven
Published: December 2023

To enable large
in silico
trials and personalized model predictions on clinical timescales, it is imperative that models can be constructed quickly and reproducibly. First, we aimed to overcome the challenges of constructing cardiac models at scale through developing a robust, open-source pipeline for bilayer and volumetric atrial models. Second, we aimed to investigate the effects of fibres, fibrosis and model representation on fibrillatory dynamics. To construct bilayer and volumetric models, we extended our previously developed coordinate system to incorporate transmurality, atrial regions and fibres (rule-based or data driven diffusion tensor magnetic resonance imaging (MRI)). We created a cohort of 1000 biatrial bilayer and volumetric models derived from computed tomography (CT) data, as well as models from MRI, and electroanatomical mapping. Fibrillatory dynamics diverged between bilayer and volumetric simulations across the CT cohort (correlation coefficient for phase singularity maps: left atrial (LA) 0.27 ± 0.19, right atrial (RA) 0.41 ± 0.14). Adding fibrotic remodelling stabilized re-entries and reduced the impact of model type (LA: 0.52 ± 0.20, RA: 0.36 ± 0.18). The choice of fibre field has a small effect on paced activation data (less than 12 ms), but a larger effect on fibrillatory dynamics. Overall, we developed an open-source user-friendly pipeline for generating atrial models from imaging or electroanatomical mapping data enabling
in silico
clinical trials at scale (
https://github.com/pcmlab/atrialmtk
).
Simultaneous data assimilation and cardiac electrophysiology model correction using differentiable physics and deep learning
Authors: Kashtanova Victoriya , Pop Mihaela , Ayed Ibrahim , Gallinari Patrick , Sermesant Maxime
Published: December 2023

Modelling complex systems, like the human heart, has made great progress over the last decades. Patient-specific models, called ‘digital twins’, can aid in diagnosing arrhythmias and personalizing treatments. However, building highly accurate predictive heart models requires a delicate balance between mathematical complexity, parameterization from measurements and validation of predictions. Cardiac electrophysiology (EP) models range from complex biophysical models to simplified phenomenological models. Complex models are accurate but computationally intensive and challenging to parameterize, while simplified models are computationally efficient but less realistic. In this paper, we propose a hybrid approach by leveraging deep learning to complete a simplified cardiac model from data. Our novel framework has two components, decomposing the dynamics into a physics based and a data-driven term. This construction allows our framework to learn from data of different complexity, while simultaneously estimating model parameters. First, using
in silico
data, we demonstrate that this framework can reproduce the complex dynamics of cardiac transmembrane potential even in the presence of noise in the data. Second, using
ex vivo
optical data of action potentials (APs), we demonstrate that our framework can identify key physical parameters for anatomical zones with different electrical properties, as well as to reproduce the AP wave characteristics obtained from various pacing locations. Our physics-based data-driven approach may improve cardiac EP modelling by providing a robust biophysical tool for predictions.
Chamber-specific wall thickness features in human atrial fibrillation
Authors: Zhao Jichao , Kennelly James , Nalar Aaqel , Kulathilaka Anuradha , Sharma Roshan , Bai Jieyun , Li Ning , Fedorov Vadim V.
Published: December 2023

Persistent atrial fibrillation (AF) is not effectively treated due to a lack of adequate tools for identifying patient-specific AF substrates. Recent studies revealed that in 30–50% of patients, persistent AF is maintained by localized drivers not only in the left atrium (LA) but also in the right atrium (RA). The chamber-specific atrial wall thickness (AWT) features underlying AF remain elusive, though the important role of AWT in AF is widely acknowledged. We aimed to provide direct evidence of the existence of distinguished RA and LA AWT features underlying AF drivers by analysing functionally and structurally mapped human hearts
ex vivo
. Coronary-perfused intact human atria (
n
= 7, 47 ± 14 y.o.; two female) were mapped using panoramic near-infrared optical mapping during pacing-induced AF. Then the hearts were imaged at approximately 170 µm
3
resolution by 9.4 T gadolinium-enhanced MRI. The heart was segmented, and 3D AWT throughout atrial chambers was estimated and analysed. Optical mapping identified six localized RA re-entrant drivers in four hearts and four LA drivers in three hearts. All RA AF drivers were anchored to the pectinate muscle junctions with the crista terminalis or atrial walls. The four LA AF drivers were in the posterior LA. RA (
n
= 4) with AF drivers were thicker with greater AWT variation than RA (
n
= 3) without drivers (5.4 ± 2.6 mm versus 5.0 ± 2.4 mm,
T
-test
p
< 0.05;
F
-test
p
< 0.05). Furthermore, AWT in RA driver regions was thicker and varied more than in RA non-driver regions (5.1 ± 2.5 mm versus 4.4 ± 2.2 mm,
T
-test
p
< 0.05;
F
-test
p
< 0.05). On the other hand, LA (
n
= 3) with drivers was thinner than the LA (
n
= 4) without drivers. In particular, LA driver regions were thinner than the rest of LA regions (3.4 ± 1.0 mm versus 4.2 ± 1.0 mm,
T
-test
p
< 0.05). This study demonstrates chamber-specific AWT features of AF drivers. In RA, driver regions are thicker and have more variable AWT than non-driver regions. By contrast, LA drivers are thinner than non-drivers. Robust evaluation of patient-specific AWT features should be considered for chamber-specific targeted ablation.
Brevibacillus ruminantium sp. nov., isolated from cow faeces
Authors: Kim Seunghwan , Heo Jun , Kwon Soon-Wo , Lee Daseul , Han Byeong-Hak , Hong Seung-Beom , Kim Yiseul
Published: December 2023

An aerobic, Gram-stain-positive, rod-shaped, endospore-forming bacterial strain, designated BB3-R1T, was isolated from cow faeces sampled in Daejeon, Republic of Korea. Growth was observed at 25–45 °C (optimum, 35–40 °C) and pH 7.0–9.0 (optimum, pH 8.0), with up to 3 % (w/v) NaCl (optimum, 0 % NaCl). blast analysis of 16S rRNA gene sequences revealed the highest sequence similarity of strain BB3-R1T to

Brevibacillus borstelensis

NRRL NRS-818T (98.8 %) followed by

Brevibacillus panacihumi

JCM 15085T (97.5 %). According to 16S rRNA gene and whole-genome based phylogenetic trees, strain BB3-R1T clustered with

Brevibacillus composti

FJAT-54423T and

B. borstelensis

NRRL NRS-818T. OrthoANI and dDDH values of strain BB3-R1T with the closely related strains were lower than 77.5 and 26.8 %, respectively. The major menaquinones and polar lipids of the strain were MK-7 and phosphatidylmonomethylethanolamine, diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine, respectively. The major fatty acids (>10 %) were C14 : 0 iso, C15 : 0 iso, C15 : 0 anteiso and C16 : 1 ω7c alcohol. The cell-wall peptidoglycan contained cross-linked meso-diaminopimelic acid (type A1 gamma). The phenotypic, chemotaxonomic and genotypic data obtained in this study showed that the strain represents a novel species of the genus

Brevibacillus

, for which the name Brevibacillus ruminantium sp. nov. (type strain BB3-R1T=KACC 22663T=NBRC 115962T) is proposed.
A distinctive evolution of alveolar T cell responses is associated with clinical outcomes in unvaccinated patients with SARS-CoV-2 pneumonia
Authors: Markov Nikolay S. , Ren Ziyou , Senkow Karolina J. , Grant Rogan A. , Gao Catherine A. , Malsin Elizabeth S. , Sichizya Lango , Kihshen Hermon , Helmin Kathryn A. , Jovisic Milica , Arnold Jason M. , Pérez-Leonor Xóchitl G. , Abdala-Valencia Hiam , Swaminathan Suchitra , Nwaezeapu Julu , Kang Mengjia , Rasmussen Luke , Ozer Egon A. , Lorenzo-Redondo Ramon , Hultquist Judd F. , Simons Lacy M. , Rios-Guzman Estefany , Misharin Alexander V. , Wunderink Richard G. , Budinger G.R. Scott , Singer Benjamin D. , Morales-Nebreda Luisa ,   The NU SCRIPT Study Investigators
Published: December 2023

Pathogen clearance and resolution of inflammation in patients with pneumonia require an effective local T cell response. Nevertheless, local T cell activation may drive lung injury, particularly during prolonged episodes of respiratory failure characteristic of severe SARS-CoV-2 pneumonia. While T cell responses in the peripheral blood are well described, the evolution of T cell phenotypes and molecular signatures in the distal lung of patients with severe pneumonia caused by SARS-CoV-2 or other pathogens is understudied. Accordingly, we serially obtained 432 bronchoalveolar lavage fluid samples from 273 patients with severe pneumonia and respiratory failure, including 74 unvaccinated patients with COVID-19, and performed flow cytometry, transcriptional, and T cell receptor profiling on sorted CD8+and CD4+T cell subsets. In patients with COVID-19 but not pneumonia secondary to other pathogens, we found that early and persistent enrichment in CD8+and CD4+T cell subsets correlated with survival to hospital discharge. Activation of interferon signaling pathways early after intubation for COVID-19 was associated with favorable outcomes, while activation of NF-κB-driven programs late in disease was associated with poor outcomes. Patients with SARS-CoV-2 pneumonia whose alveolar T cells preferentially targeted the Spike and Nucleocapsid proteins tended to experience more favorable outcomes than patients whose T cells predominantly targeted the ORF1ab polyprotein complex. These results suggest that in patients with severe SARS-CoV-2 pneumonia, alveolar T cell interferon responses targeting structural SARS-CoV-2 proteins characterize patients who recover, yet these responses progress to NF-κB activation against non-structural proteins in patients who go on to experience poor clinical outcomes.
Longitudinal associations between weight indices, cognition, and mental health from childhood to early adolescence
Authors: Li Zhaolong Adrian , Ray Mary Katherine , Gu Yueping , Barch Deanna M. , Hershey Tamara
Published: December 2023

Childhood obesity has been associated with lower cognitive performance and worse mental health in cross-sectional studies. However, it is unclear whether these findings extend longitudinally and in what causal direction. Using data from the Adolescent Brain Cognitive Development (ABCD) Study (maximum analytical n = 6671, 48.3% girls, 42.8% non-White), we examined how body mass index (BMI) at baseline (ages 9-11) relate prospectively to changes in cognition or psychopathology across the 2 years thereafter, and vice versa. Cognitive tests included the National Institutes of Health Toolbox Cognition Battery, Little Man Task of mental rotation, and Rey Auditory Verbal Learning Test. Psychopathology was assessed using caregiver-reported Child Behavior Checklist. Linear mixed models adjusted for sociodemographic and developmental covariates indicated that lower baseline performance on most cognitive tests was associated with greater longitudinal BMI gain (eg, 1 point lower than median on Picture Vocabulary corresponded to 0.012 kg/m2[1.6%; 95% CI, 0.008 to 0.016 kg/m2] more annual BMI gain,PFDR< .001), whereas baseline BMI was unrelated to longitudinal changes in cognition (PFDR≥ .12; including after considering practice effects). Greater broad-spectrum psychopathology at baseline was associated with increased BMI gain (eg, each endorsement of externalizing problems than none corresponded to 0.015 kg/m2[2.2%; 95% CI, 0.009 to 0.021 kg/m2] more annual BMI gain,PFDR< .001) and, reciprocally, greater baseline BMI was linked specifically to more longitudinal withdrawn/depressed and depression problems (0.010 [22%; 95% CI, 0.004 to 0.016] and 0.011 [15%; 95% CI, 0.004 to 0.017] more problems annually per 1 kg/m2above median BMI,PFDR= .003 and .008). The associations did not differ in boys vs. girls (PFDR≥ .40), and remained stable with waist circumference as the weight index and in subgroups of participants without weight-altering medications or common baseline psychiatric diagnoses. Our longitudinal findings expand previous cross-sectional works and highlight the importance of cognitive and mental health to children’s weight development and links between weight and depression.
Major depression is not an inflammatory disorder: depletion of the compensatory immunoregulatory system is a hallmark of a mild depression phenotype
Authors: Maes Michael , Vasupanrajit Asara , Jirakran Ketsupar , Zhou Bo , Tunvirachaisakul Chavit , Almulla Abbas F.
Published: December 2023

Background

Major depression comprises two discrete subtypes, major (MDMD) and simple (SDMD) dysmood disorder. MDMD, but not SDMD, patients were identified to have highly sensitized cytokine/growth factor networks using stimulated whole blood cultures. However, no information regarding serum cytokines/chemokines/growth factors in SDMD is available.

Objectives

This case-control study compares 48 serum cytokines/chemokines/growth factors in academic students with SDMD (n=64) and first episode (FE)-SDMD (n=47) to those of control students (n=44) using a multiplex assay.

Findings

Both FE-SDMD and SDMD exhibit a notable inhibition of immune profiles, such as the compensatory immunoregulatory response system (CIRS) and alternative M2 macrophage and T helper-2 (Th-2) profiles. We observed a substantial reduction in the serum concentrations of five proteins: interleukin (IL)-4, IL-10, soluble IL-2 receptor (sIL-2R), IL-12p40, and macrophage colony-stimulating factor. A significant proportion of the variability observed in suicidal behaviors (26.7%) can be accounted for by serum IL-4, IL-10, and sIL-2R (all decreased), and CCL11 (eotaxin) and granulocyte CSF (both increased). The same biomarkers (except for IL-10), accounted for 25.5% of the variance in SDMS severity. A significant correlation exists between decreased levels of IL-4 and elevated ratings of the brooding type of rumination.

Conclusions

The immune profile of SDMD and FE-SDMD exhibits a significant deviation from that observed in MDMD, providing additional evidence that SDMD and MDMD represent distinct phenotypes. SDMD is characterized by the suppression of the CIRS profile, which signifies a disruption of immune homeostasis and tolerance, rather than the presence of an inflammatory response.
Asymptomatic SARS-CoV-2 infections tend to occur less frequently in developed nations
Authors: Chowdhury Shreya , Tiwari Akshay , James Ananthu , Chatterjee Budhaditya , Dixit Narendra M.
Published: December 2023

Unlike severe infections, asymptomatic infections occur independently of healthcare access and reflect the natural immunity to SARS-CoV-2. What determines their prevalence,ψ, and its variation across nations is unknown. We conducted a systematic review of serosurveys performed on samples representative of national populations before vaccination and the emergence of variants. The studies that met our selection criteria together sampled 4,58,489 individuals and yielded estimates ofψin 33 nations. Using random-effects modeling, we found the pooled globalψto be 45.3% (95% CI: 33.6%-57.5%).ψvaried widely across nations (range: 6%-96%;I2=99.7%), highlighting the enormous underlying variation in the natural immunity to SARS-CoV-2. Performing meta-regression with national-level metrics, we found that the human development index (HDI) was negatively correlated withψ(p=10−13;R2=65.5%). More developed nations thus experienced less frequent asymptomatic infections on average. These findings have implications for unraveling the origins of asymptomatic infections and for future pandemic preparedness.
What influences ambulance clinician decisions to pre-alert Emergency Departments: a qualitative exploration of decision-making in three UK Ambulance Services
Authors: O’Hara Rachel , Sampson Fiona , Long Jaqui , Coster Joanne , Pilbery Richard
Published: December 2023

Background

Ambulance clinicians use pre-alerts to inform receiving hospitals of the imminent arrival of a time-critical patient considered to require immediate attention, enabling the receiving Emergency Department or other clinical area to prepare. Pre-alerts are key to ensuring immediate access to appropriate care, but unnecessary pre-alerts can divert resources from other patients and fuel ‘pre-alert fatigue’ amongst ED staff. This research aims to provide a better understanding of pre-alert decision-making practice.

Methods

Semi-structured interviews were conducted with 34 ambulance clinicians from three ambulance services and 40 ED staff from six receiving EDs. Observation (162 hours) of responses to pre-alerts (n=143, call-to-handover) was also conducted in the six EDs. Interview transcripts and observation notes were imported into NVIVO and analysed using thematic analysis.

Findings

Pre-alert decisions involve rapid assessment of clinical risk based on physiological observations, clinical judgement, and perceived risk of deterioration, with reference to pre-alert guidance. Clinical experience (pattern recognition and intuition) and confidence helped ambulance clinicians to understand which patients required immediate ED care upon arrival or were at highest risk of deterioration. Ambulance clinicians primarily learned to pre-alert ‘on the job’ and via informal feedback mechanisms, including the ED response to previous pre-alerts. Availability and access to clinical decision support was variable, and clinicians balanced the use of guidance and protocols with concerns about retention of clinical judgement and autonomy. Differences in pre-alert criteria between ambulance services and EDs created difficulties in deciding whether to pre-alert and was particularly challenging for less experienced clinicians.

Conclusion

We identified potentially avoidable variation in decision-making, which has implications for patient care and emergency care resources, and can create tension between the services. Consistency in practice may be improved by greater standardisation of guidance and protocols, training and access to performance feedback, and cross-service collaboration to minimise potential sources of tension.
Explainable machine learning-based prediction of depression severity in medical students
Authors: Liu Dianhao , Chen Zequn , Marrero Wesley J. , Jacobson Nicholas C. , Thesen Thomas
Published: December 2023

Importance

Medical students exhibit depression or depressive symptoms at a higher rate than the general population, with a potential for reduced academic performance and increased risk of suicide and physical health problems. Understanding the factors contributing to depression severity is critical for early detection and creating support systems personalized to the mental health challenges of medical students.

Objective

To predict and identify the key biopsychosocial factors influencing the severity of depression in medical students across the United States using explainable machine learning algorithms.

Design

This prognostic study is built upon survey data from the Healthy Minds Study student survey spanning the academic years of 2009 to 2021 across the US. Students’ depression severity is measured using the Patient Health Questionnaire-9 (PHQ-9).

Setting

All undergraduate and graduate students from the American universities participating in the Healthy Minds Study are included in our study. While our target cohort is composed of medical students only, we include undergraduate and graduate students in our population to increase the size of our data during the machine learning training process.

Participants

A total of 167,999 students completed the PHQ-9 inventory, including 2,174 medical students.

Main Outcome and Measure

Prediction accuracy is measured by the mean absolute error across a previously unseen cohort of medical students. This metric estimates the average absolute difference between the predicted and actual responses of the general medical student population.

Results

By testing several predictive machine learning algorithms, we found that a sequence of binary XGBoost models achieved the lowest mean absolute error amongst all interpretable algorithms. Depression severity was best predicted by factors in the following order of importance: 1. history of depressive diagnosis, 2. disordered eating behaviors, 3. current financial stress, and 4. younger age.

Conclusions and Relevance

By identifying predictors of student risk for developing depressive symptoms, our findings can help facilitate early identification of medical students at risk for developing depressive symptoms and providing them with early support and proactive strategies to prevent future depressive episodes.
cCMP and cUMP stimulate the acid phosphatase activity of AphA inHaemophilus influenzae
Authors: Kronborg Kristina , Zhang Yong Everett
Published: December 2023

We recently detailed the competitive inhibition of cyclic AMP (cAMP) on three periplasmic enzymes, AphA, NadN, and Hel, inHaemophilus influenzaeRd KW20. This inhibitory effect is vital for orchestrating the nutritional growth and competence development in KW20. Here, we extended the study to the three other second messengers, i.e., cyclic GMP, cyclic UMP, and cyclic CMP, each sharing structural similarities with cAMP. Notably, cGMP competitively inhibits AphA’s acid phosphatase activity akin to cAMP. In contrast, both cUMP and cCMP stimulate AphA’s phosphatase activity in a dose-dependent manner. This novel finding underscores the intriguing opposing effects of cyclic purine and pyrimidine nucleotides on AphA, suggesting potential intricate biological crosstalk among these second messengers.
DNA binding and bridging by human CtIP in the healthy and diseased states
Authors: Balaji Shreya Lokanathan , De Bragança Sara , Balaguer-Pérez Francisco , Northall Sarah , Wilkinson Oliver , Aicart-Ramos Clara , Seetaloo Neeleema , Sobott Frank , Moreno-Herrero Fernando , Dillingham Mark Simon
Published: December 2023

The human DNA repair factor CtIP helps to initiate the resection of double-stranded DNA breaks for repair by homologous recombination, in part through its ability to bind and bridge DNA molecules. However, CtIP is a natively disordered protein that bears no apparent similarity to other DNA-binding proteins and so the structural basis for these activities remains unclear. In this work, we have used bulk DNA binding, single molecule tracking, and DNA bridging assays to study wild-type and variant CtIP proteins to better define the DNA binding domains and the effects of mutations associated with inherited human disease. Our work identifies a monomeric DNA-binding domain in the C-terminal region of CtIP. CtIP binds non-specifically to DNA and can diffuse over thousands of nucleotides. CtIP-mediated bridging of distant DNA segments is observed in single-molecule magnetic tweezers experiments. However, we show that binding alone is insufficient for DNA bridging, which also requires tetramerization via the N-terminal domain. Variant CtIP proteins associated with Seckel and Jawad syndromes display impaired DNA binding and bridging activities. The significance of these findings in the context of facilitating DNA break repair is discussed.

Significance Statement

CtIP helps to repair broken chromosomes through its ability to bind and bridge DNA molecules. We studied the structural and biochemical basis for these activities and how they are affected by hereditary CtIP mutations associated with developmental disorders. We discovered a minimal domain in the C-terminal region of CtIP which supports DNA binding as a monomer. DNA binding is non-specific and facilitates 1D diffusion, but binding alone is insufficient for intermolecular tethering of DNA molecules which requires tetramerization of CtIP via N-terminal coiled-coil domains. All disease variants tested displayed impaired DNA bridging activity. These results have important implications for understanding the role of CtIP as a hub protein for DNA break repair and its dysfunction in human disease.
Niche signalling regulates eIF3d1 phosphorylation to promote distinct modes of translation initiation in stem and differentiating cells
Authors: Wang Ruoxu , Roiuk Mykola , Storer Freya , Teleman Aurelio A. , Amoyel Marc
Published: December 2023

Stem cells have the unique ability among adult cells to give rise to cells of different identities. To do so, they must change gene expression in response to environmental signals. Much work has focused on how transcription is regulated to achieve these changes, however in many cell types, transcripts and proteins correlate poorly, indicating that post-transcriptional regulation is important. To assess how translational control can influence stem cell fate, we use the Drosophila testis as a model. The testis niche secretes a ligand to activate the JAK/STAT pathway in two stem cell populations, germline stem cells (GSCs) and somatic cyst stem cells (CySCs). We find that global translation rates are high in CySCs and decrease during differentiation, and that JAK/STAT signalling regulates translation. To determine how translation was regulated, we knocked down translation initiation factors and found that the cap binding complex, eIF4F, is dispensable in differentiating cells, but is specifically required in CySCs for self-renewal, acting downstream of JAK/STAT activity. Moreover, we identify eIF3d1 as a key regulator of CySC fate, and show that its phosphorylation is critical to maintain CySC self-renewal. We further show that Casein Kinase II, which controls eIF3d1 phosphorylation, is sufficient to restore CySC function in the absence of JAK/STAT. We propose a model in which niche signals regulate a specific translation programme in which only some mRNAs are translated, through regulation of eIF3d phosphorylation. The mechanism we identify allows stem cells to switch between modes of translation, adding a layer of regulation on top of transcription and providing cells with the ability to rapidly change gene expression upon receiving external stimuli.
Ser/Thr Phosphorylation ofMycobacterium tuberculosisType II Rel TA module by Protein Kinase K interferes with toxin neutralization: A novel mode of TA regulation
Authors: Sarah Shafinaz Rahman , Garg Abhishek , Korch Shaleen , Gupta Amita , Malhotra Vandana
Published: December 2023

Toxin-Antitoxin (TA) modules represent genetic elements implicated in bacterial persistence and antibiotic tolerance. Remarkably,Mycobacterium tuberculosisencodes 90+ TA modules, the majority of which are Type II TA comprising of a toxin component and an antitoxin counterpart that neutralizes the toxin. Upon exposure to stress, the antitoxin is degraded, releasing the toxin which then acts to halt cellular growth. Given that TA modules dictate social behavior of a population, we hypothesize that their regulation must be exquisitely controlled to avoid superfluous growth inhibition and initiation of persistence. However, the regulation and coordination of TA modules is poorly understood. Herein, we describe for the first time, a novel regulatory mechanism for Type II TA modules involving post-translational modification (PTM). Using computational tools, we observed that over 85 % of theM. tuberculosisTA proteins possess potential Ser/Thr phosphosites highlighting them as putative substrates forM. tuberculosisSer/Thr protein kinases (STPK). We demonstrate that members of the RelBE family are subjected toO-phosphorylation by PknK, a stress-responsive growth regulatory STPK. Mass spectrometry confirmed multiple sites of PknK-mediated phosphorylation in the RelJK TA module. To gain insights into the functional impact of this PTM, we conductedin vitrobinding and phenotypic growth studies with the wild type and mutant RelJK proteins. Our findings indicate that phosphorylation of Thr77 residue in RelK toxin compromises its binding to the RelJ antitoxin. These results suggest a potential role forO-phosphorylation in influencing the interaction dynamics of the TA module components.

Importance

Bacterial pathogens rely on the phenomenon of persistence as a survival strategy to combat the adverse environmental conditions encountered during infection. As a stochastic process, the driving force(s) that potentiate the formation of persisters in a bacterial population are largely unclear. This study is a step towards the discovery of intricate regulatory mechanisms that coordinate a synchronized TA cellular program. We propose a model wherein the TA module is regulated post translationally, specifically via Ser/Thr phosphorylation disrupting the interaction between the toxin and antitoxin proteins as a mechanism to regulate TA function.
Caulobacter crescentusRNase E condensation contributes to autoregulation and fitness
Authors: Nandana Vidhyadhar , Al-Husini Nadra , Vaishnav Arti , Dilrangi Kulathungage H. , Schrader Jared M.
Published: December 2023

RNase E is the most common RNA decay nuclease in bacteria, setting the global mRNA decay rate and scaffolding formation of the RNA degradosome complex and BR-bodies. To properly set the global mRNA decay rate, RNase E fromEscherichia coliand neighboring γ-proteobacteria were found to autoregulate RNase E levels via the decay of its mRNA’s 5’ UTR. While the 5’ UTR is absent from other groups of bacteria in the Rfam database, we identified that the α-proteobacteriumCaulobacter crescentusRNase E contains a similar 5’ UTR structure that promotes RNase E autoregulation. In both bacteria, the C-terminal IDR of RNase E is required for proper autoregulation to occur, and this IDR is also necessary and sufficient for RNase E to phase-separate, generating BR-bodies. Usingin vitropurified RNase E, we find that the IDR’s ability to promote phase-separation correlates with enhanced 5’ UTR cleavage, suggesting that phase-separation of RNase E with the 5’ UTR enhances autoregulation. Finally, using growth competition experiments we find that a strain capable of autoregulation rapidly outcompetes a strain with a 5’ UTR mutation that cannot autoregulate, suggesting autoregulation promotes optimal cellular fitness.
The potential of exoskeletons in construction: barriers and challenges
Authors: Lindhard Søren Munch , Lassen Astrid Heidemann , Cheng Yang , Musso Matteo , Wang Geng , Bai Shaoping
Published: December 2023

Purpose

Exoskeletons are moving into industries with the potential to reduce muscle strains and prevent occupational injuries. Although exoskeletons have been designed and tested in laboratory settings, rare empirical studies of their application in construction have been reported. Therefore, the purpose of this study is on in a real-life setting testing the applicability of adopting exoskeletons in the construction industry.

Design/methodology/approach

A feasibility study of exoskeletons in construction is conducted by testing a passive exoskeleton, designed for shoulder support. Five bricklayers tested in a two-month period the exoskeleton, each wearing it for a three-day period while carrying out normal work activities. Test data in terms of interviews were collected and analyzed using qualitative content analysis.

Findings

The application of exoskeletons in construction revealed several limitations, where the two primary ones are the exoskeleton is not designed while considering the tasks of a bricklayer causing several challenges and the exoskeleton only supports a single upward motion while limiting other movements and even counteracted when a downward movement was necessary.

Originality/value

The identified challenges could easily have been revealed by coupling the design and testing of exoskeletons to actual application. Thus, the design approach needs to be reversed. Instead of designing an exoskeleton to support a specific body part or motion and then identifying where it is applicable, it should target specific industries and focus on the actual work and movements and the necessary support. As part of the change, the design metrics should be reevaluated to reflect the work to support.
How to predict the entry mode of international construction contractor: a case-based reasoning approach
Authors: Li Huiling , Yuan Wenya , Xu Jianzhong
Published: December 2023

Purpose

This study aimed to identify a specific taxonomy of entry modes for international construction contractors and to develop a decision-making mechanism based on case-based reasoning (CBR) to facilitate the selection of the most suitable entry modes.

Design/methodology/approach

According to the experience orientation of the construction industry, a CBR entry mode decision model was established, and based on successful historical cases, a two-step refinement process was carried out to identify similar situations. Then the validity of the model is proved by case analysis.

Findings

This study identified an entry mode taxonomy for international construction contractors (ICCs) and explored their decision-making mechanisms. First, a two-dimension model of entry mode for ICCs was constructed from ownership and value chain dimensions; seven common ICC entry modes were identified and ranked according to market commitment. Secondly, this study reveals the impact mechanism of the ICC entry mode from two aspects: the external environment and enterprise characteristics. Accordingly, an entry mode decision model is established.

Practical implications

Firstly, sorting out the categories of entry mode in the construction field, which provide an entry mode list for ICCs to select. Secondly, revealing the impact mechanism of ICC entry mode, which proposes a systematic decision-making system for the selection of ICC entry mode. Thirdly, constructing a CBR entry mode decision-making model from an empirical perspective, which offers tool support and reduces transaction costs in the decision-making process.

Originality/value

The study on entry modes for ICCs is still in the preliminary exploratory stage. The authors investigate the entry mode categories and decision-making mechanisms for ICCs based on Uppsala internationalization process theory. It widens the applied scope of Uppsala and promotes cross-disciplinary integration. In addition, the authors creatively propose a two-stage retrieval mechanism in the CBR model, which considers the order of decision variables. It refines the influence path of the decision variables on ICCs' entry mode.