bluuebunny/crossref_metadata_2025 huggingface dataset:
A case of colonic MALT lymphoma with intra-abdominal abscess and lung metastasis: A case report
Authors: Lee Kangkook , Lee Jin Wook , Jung Hye Ra , Park Myeongsoon , Cho Kwang Bum , Lee Ju Yup
Published: February 2024

Rationale:

Colonic mucosa-associated lymphoid tissue (MALT) lymphoma is an unusual subtype comprising only 2.5% of all MALT lymphomas. Most cases of colonic MALT lymphoma are diagnosed at an early stage. Therefore, the clinical features of advanced-stage colonic MALT lymphoma have seldom been reported, and the endoscopic findings are not well established. In this study, we report the clinical and endoscopic characteristics of stage IV colonic MALT lymphoma and highlight the importance of repeat biopsy to figure out this rare disease.

Patient concerns:

The patient was a 68-year-old male complaining of hematochezia and lower left quadrant abdominal pain for the past 3 days.

Diagnoses:

The patient had 3 masses and friable mucosal lesions in the colon. With the first colonoscopy and biopsy, he was initially diagnosed as having eosinophilic colitis. However, the first treatment with steroids did not show any response. Because of atypical clinical features and colonoscopic findings, a second colonoscopy and a repeat biopsy were performed, and the results were consistent with colonic MALT lymphoma arising in the colon. The patient was finally diagnosed with stage IV colonic MALT lymphoma accompanied by multiple distant metastases.

Interventions and outcomes:

The patient started to receive chemotherapy with a combination regimen of cyclophosphamide, vincristine, and prednisolone. The follow-up study after 3 months showed stable disease status based on response evaluation criteria in solid tumors.

Lessons:

This case report presents atypical clinical characteristics and colonoscopic findings of stage IV colonic MALT lymphoma. Clinical suspicion and repeat biopsy should be considered to diagnose this rare and diagnostically challenging cancer.
Disseminated disease caused by Mycobacterium marseillense: A case report and literature review
Authors: Cheng Ji , Qu Jun-Yan , Hamblin Michael R. , Hao Dan , Wen Xiang
Published: February 2024

Rationale:

Among numerous types of nontuberculous mycobacterial infections, Mycobacterium avium complex is a related group of species, which can cause various diseases in humans. Mycobacterium marseillense is a member of the Mycobacterium avium complex, which accounts for only a small proportion of species, but causes rare diseases affecting the lungs, lymph nodes, skin, and tendon sheath. So far, very few cases have been reported.

Patient concerns:

A 76-year-old male of peculiar skin infection. Metagenomic Next Generation Sequencing and bacterial culture of skin secretions revealed M marseillense. To the best of our knowledge, we report the first patient diagnosed with disseminated M marseillense infection. Here, we identified only 8 other reports of patients with M marseillense infection.

Diagnoses:

Disseminated M marseillense infection.

Interventions:

The patient was treated with clarithromycin, rifampicin, moxifloxacin, and ethambutol.

Outcomes:

The skin lesions of the patient showed significant improvement, and his pruritus and limb pain were notably reduced after 7 months of follow-up.

Lessons:

Metagenomic Next Generation Sequencing may be a useful tool to diagnose M marseillense infection, but the results should be confirmed by culture and mycobacterial identification.
The displaced polymer clamp entered the duodenum causing an abscess: A case report
Authors: Yang Yong Qiang , Gou Wen Bin
Published: February 2024

Rationale:

The Hem-o-lok clip, made from a nonabsorbable polymer, and its predecessor the metal ligation clip have been used widely for laparoscopic or robot-assisted surgery to ligate the cystic duct after a cholecystectomy, to ligate the appendix after an appendectomy, or control hemorrhage or on occasion to occlude a fistula or enterotomy. Displacement of these ligation clips to distant sites is an extremely rare complication in clinical practice.

Patient concerns:

The patient is a 67-year old female who sought medical attention for 3 days due to worsening intermittent upper abdominal pain and poor appetite. Gastroscopy showed both an ulcer and the presence of a foreign object embedded in the anterior wall of the duodenal bulb, consistent with what looked like a polymer-based ligation clip. After removal of the foreign body, which turned out to be a remnant of the polymer clip, no further pus was seen, but fresh granulomatous tissues were seen at the base.

Diagnoses:

a polymer-based clip-induced duodenal bulb erosion with a local contained enterically draining abscess.

Interventions:

The patient recovered after removing foreign bodies under gastroscopy and receiving anti infection treatment.

Outcomes:

The patient recovered after removing foreign bodies under gastroscopy and receiving anti infection treatment.

Lessons:

In laparoscopic cholecystectomy, attention should be paid to the correct surgical techniques, possibly by decreasing the number of such clips used or considering use of absorbable clips, ligature wires, ligation with absorbable suture material, or ultrasonic resection, all of which can be used for clipless cholecystectomy.
Radical resection of hepatic alveolar echinococcosis combined with cystic echinococcosis: A case report
Authors: Ma Xiaoguang , Su Wei , Wang Xiao , Zhao Rui
Published: February 2024

Rationale:

Hepatic Echinococcosis, is a zoonotic Parasitic disease with a worldwide distribution. Clinical cases of alveolar echinococcosis combined with cystic echinococcosis infection are extremely rare.

Patient concerns:

A 58-year-old patient had found liver occupying lesions for more than 2 years. A left hepatic alveolar hydatid was found, occupying the entire left half of the liver, with a size of approximately 6.7 cm × 10.9 cm × 8.1 cm. The size of the right liver is about 9 × 8 cm cystic hydatid, mainly located in the S5 segment of the liver. Abdominal examination: the upper abdomen is swollen, and a hard mass can be touched under the right rib margin, with tenderness and no rebound pain. The bowel sounds are normal.

Diagnoses:

Abdominal MR shows an increase in liver volume and irregular morphology, with patchy abnormal signal shadows visible in the left lobe of the liver, with a range of approximately 6.7 cm × 10.9 cm × 8.1 cm, low signal on T1WI, low signal on T2WI and FS-T2WI, slightly high signal on diffusion weighted imaging, high signal on apparent diffusion coefficient, no significant enhancement of the lesion after enhancement. In addition, there is a clump like abnormal signal shadow visible in the right lobe of the liver, with a size of approximately 7.9 cm × 7.3 cm × 7.9 cm, low signal on T1WI, mixed high signal on T2WI, high signal on diffusion weighted imaging, mixed signal on apparent diffusion coefficient. Consider: Left lobe alveolar echinococcosis, and right lobe cystic echinococcosis (CE III type).

Interventions:

A radical resection was performed, including expanded left hemi-hepatectomy, cholecystectomy, right hepatic lesion resection, partial right hepatic duct resection with right hepatic duct jejunostomy.

Outcomes:

The wound healed well after resection. There was no recurrence of TC after 4 years follow-up.

Lessons:

The co-infection of alveolar echinococcosis and cystic echinococcosis in a patient is an exceedingly rare occurrence. Radical resection is the only curative treatment.
Mini review: A reevaluation of nutritional vitamin D in the treatment of chronic kidney disease
Authors: Shen Yingjing
Published: February 2024

Chronic kidney disease-mineral and bone disorder is a syndrome of mineral and bone metabolism abnormalities caused by chronic kidney disease. Osteoporosis is a systemic metabolic bone disease characterized by low bone mass, disruption of bone microstructure, increased brittleness, and a higher propensity for fractures. Both of these conditions significantly affect bone metabolism and substantially increase the risk of fractures. Nutritional vitamin D is an essential trace element in the human body and an important fat-soluble vitamin. One crucial physiological role of nutritional vitamin D is to achieve mineral-bone metabolism balance by regulating calcium homeostasis. This review summarized the metabolism of vitamin in normal population and its specificity in chronic kidney disease. Over the years, the understanding and application of vitamin D in patients with chronic renal failure is changing. As people pay more attention to hypercalcemia, vascular calcification, osteoporosis, nutritional vitamin D has come into people’s attention again. More and more studies are discussing how to prescribe vitamin D supplementation in hemodialysis patients.
Clinical implication of thoracic skeletal muscle volume as a predictor of ventilation-weaning failure in brain-injured patients: A retrospective observational study
Authors: Oh Jimi , Lim Hyun , Jeong Chang Won , Kim Min Su , Lee Jinseok , Kang Wu Seong , An Ui Ri , Park Joo Un , Ahn Youngick , Kim Youe Ree , Park Chul
Published: February 2024

Sarcopenia, a generalized loss of skeletal muscle mass that is primarily evident in the respiratory musculature, is associated with adverse outcomes in critically ill patients. However, the relationship between sarcopenia and ventilation-weaning outcomes has not yet been fully studied in patients with brain injuries. In this study, we examined the effect of reduced respiratory muscle mass on ventilation weaning in patients with brain injury. This observational study retrospectively reviewed the medical records of 73 patients with brain injury between January 2017 and December 2019. Thoracic skeletal muscle volumes were measured from thoracic CT images using the institute’s three-dimensional modeling software program of our institute. The thoracic skeletal muscle volumes index (TSMVI) was normalized by dividing muscle volume by the square of patient height. Sarcopenia was defined as a TSMVI of less than the 50th sex-specific percentile. Among 73 patients with brain injury, 12 (16.5%) failed to wean from mechanical ventilation. The patients in the weaning-failure group had significantly higher sequential organ failure assessment scores [7.8 ± 2.7 vs 6.1 ± 2.2, P = .022] and lower thoracic skeletal muscle volume indexes [652.5 ± 252.4 vs 1000.4 ± 347.3, P = .002] compared with those in the weaning-success group. In multivariate analysis, sarcopenia was significantly associated with an increased risk of weaning failure (odds ratio 12.72, 95% confidence interval 2.87–70.48, P = .001). Our study showed a significant association between the TSMVI and ventilation weaning outcomes in patients with brain injury.
Causes of sudden neonatal mortality disclosed by autopsy and histopathological examination
Authors: Özdemir Kara Doğuş
Published: February 2024

The neonatal period, or the first 28 days of life, is the most vulnerable time in a child’s life. Neonatal mortality has decreased in recent years. However, this progress varies at the national level, which necessitates actual regional data from different countries to identify local handicaps for life-saving precautions. This study aimed to investigate the causes for neonatal deaths as revealed by autopsy and histopathological examinations. A retrospective cross-sectional study was designed to identify the main causes of neonatal deaths in children who were autopsied at our institution between January 1, 2014, and December 31, 2021. Children who died within the first 28 days after birth (1–28 days of age) were referred to as neonatal cases. The main causes of neonatal death in children were determined via autopsy and histopathological and toxicological examinations. Furthermore, the causes of death were classified according to their manner of death. During this period, 122 neonatal children were autopsied at our institution. This group comprised 57 girls and 65 boys. For the manner of the death, natural causes were the most common cause (n = 91, 74.5%). Among natural causes, pneumonia (n = 66) was the leading one, representing 54% of all neonatal deaths, followed by perinatal conditions (n = 16, 13.1%). One of the pioneering reasons for death was sudden, unexpected postnatal collapse (n = 24, 19.6%), which was categorized under the undetermined group considering the manner of death. Unintentional (accidental) deaths accounted for 0.8% (n = 1) of total deaths, and intentional deaths were responsible for 6 neonates (4.9%) losses. This study shows that newborn children still die from simple and treatable infectious causes, probably arising from various familial and/or public inadequacies. In addition, sudden and unexpected postnatal collapse remains an important cause of neonatal mortality that has yet to be fully resolved. This study points out valuable inferences for caregivers and competent authorities to take preventive measures to prevent avoidable neonatal deaths.
The impact of MYD88 and PIM1 in mature large B-cell non-Hodgkin lymphomas: Defining element of their evolution and prognosis
Authors: Cristian Miruna , Așchie Mariana , Mitroi Anca-Florentina , Deacu Mariana , Boșoteanu Mădălina , Bălțătescu Gabriela-Izabela , Stoica Andreea-Georgiana , Nicolau Anca-Antonela , Enciu Manuela , Crețu Ana-Maria , Caloian Andreea-Daniela , Orășanu Cristian-Ionuț , Poinăreanu Ionuț
Published: February 2024

Sequence studies of the entire exome and transcriptome of lymphoma tissues have identified MYD88 and PIM1 as involved in the development and oncogenic signaling. We aimed to determine the frequency of MYD88 and PIM1 mutations, as well as their expressions in conjunction with the clinicopathological parameters identified in mature large B-cell non-Hodgkin lymphomas. The ten-year retrospective study included 50 cases of mature large B-cell lymphoma, diagnosed at the Pathology Department of the Emergency County Hospital of Constanţa and Săcele County Hospital of Brasov. They were statistically analyzed by demographic, clinicopathological, and morphogenetic characteristics. We used a real-time polymerase chain reaction technique to identify PIM1 and MYD88 mutations as well as an immunohistochemical technique to evaluate the expressions of the 2 genes. Patients with lymphoma in the small bowel, spleen, brain, and testis had a low-performance status Eastern Cooperative Oncology Group (P = .001). The Eastern Cooperative Oncology Group performance status represented an independent risk factor predicting mortality (HR = 9.372, P < .001). An increased lactate dehydrogenase value was associated with a low survival (P = .002). The international prognostic index score represents a negative risk factor in terms of patient survival (HR = 4.654, P < .001). In cases of diffuse large B-cell lymphoma (DLBCL), immunopositivity of MYD88 is associated with non-germinal center B-cell origin (P < .001). The multivariate analysis observed the association between high lactate dehydrogenase value and the immunohistochemical expression of PIM1 or with the mutant status of the PIM1 gene representing negative prognostic factors (HR = 2.066, P = .042, respectively HR = 3.100, P = .004). In conclusion, our preliminary data suggest that the oncogenic mutations of PIM1 and MYD88 in our DLBCL cohort may improve the diagnosis and prognosis of DLBCL patients in an advanced stage.
The psychological intervention and clinical efficacy of Rosenthal effect and acupuncture bleeding on middle-aged and young patients with sudden hearing loss
Authors: Sun, Haiping , Chu, Chengmei , Wang, Xu , Gao Feng
Published: February 2024

Combining traditional Chinese medicine theory and modern medical knowledge, this study explores the pathogenesis of sudden hearing loss in middle-aged and young people. Sixty-four young and middle-aged patients with sudden hearing loss who visited a public tertiary hospital in China are chosen as experimental objects. All experimental patients are broken into an experimental group (n = 32) and a control group (n = 32). The control group receive conventional Western medicine treatment regimen. The experimental group receive select acupoint acupuncture and bloodletting combined with Rosenthal effect for psychological intervention, and both groups have a treatment course of 14 days. The changes in the patient’s condition before and after treatment are observed, and the differences in hearing threshold values, tinnitus, and dizziness clinical efficacy before and after treatment are observed and recorded. It evaluates the efficacy using the Anxiety, Depression Scale, and Hope Scale and statistically analyzes the data. The dizziness score of the experimental group decreased rapidly, the treatment onset time was shorter, and the improvement effect on dizziness symptoms was better (P < .05). After 1 month of intervention treatment, the intervention of the experimental group was better (P < .05). The hope level and self-efficacy of both groups of patients were raised in contrast with before treatment (P < .05). After 1 month, the intervention effect of the experimental group was more significant (P < .01). Both groups could improve patient ear blood circulation, but the experimental group had lower plasma viscosity, hematocrit, and red blood cell aggregation index, higher red blood cell deformation index, and more significant improvement effect (P < .05). The effective rates of improving hearing and tinnitus in the experimental group reached 87.5% and 81.5%, and the clinical treatment efficacy was better than that in the control group (P < .05). The level of depression and anxiety in the experimental group remained relatively stable, while that in the control group showed a significant rebound (P < .05). In conclusion, both groups had a certain effect in treating sudden deafness, both of which could effectively improve the patient’s hearing. But in contrast with the control group, the experimental group had better clinical efficacy, higher safety, and better psychological intervention results, which is worthy of clinical promotion.
Two successful pregnancies in a membranous nephropathy patient: Case report and literature review
Authors: Qin Congcong , Hu Zhijuan , Shi Yanan , Cui Hui , Li Jiejie
Published: February 2024

Background:

Pregnancy in patients with nephrotic syndrome presents enormous challenges to both the mother and fetus, and there are no treatment guidelines for these patients.

Methods:

We show a case of a woman with anti-PLA2R antibody-positive membranous nephropathy who did not have a kidney biopsy. Her clinical course during both pregnancies was closely followed and her medications were guided.

Results:

She gave birth to 2 healthy babies and her condition was very well controlled with the help of medication.

Conclusion:

Patients with nephrotic syndrome can have successful pregnancies after drug treatment. In addition, similar to the non-pregnant population, percutaneous kidney biopsy is not required for the diagnosis of idiopathic membranous nephropathy (IMN) in pregnant nephrotic syndrome patients with anti-PLA2R antibody positive, but the etiology of secondary MN should be excluded.
Comparison of pressure controlled, volume controlled, and volume guaranteed pressure controlled modes in prone position in patients operated for lumbar disc herniation: A randomized trial
Authors: Gunenc Ferim Sakize , Seyidova İlkana , Ozbilgin Sule , Ur Koray , Hanci Volkan
Published: February 2024

Background:

To compare pressure-controlled ventilation (PCV), volume-controlled ventilation (VCV), and pressure-controlled ventilation-volume guaranteed (PCV-VG) modes in patients undergoing spinal surgery in the prone position under general anesthesia.

Methods:

The study included 78 patients aged 20 to 80 years, American Society of Anesthesiologists 1–2, scheduled for lumbar spinal surgery. Patients included in the study were randomly divided into 3 groups Group-VCV; Group-PCV; Group-PCV-VG. Standard anesthesia protocol was applied. In addition to routine monitoring, train of four and BIS monitoring were performed. All ventilation modes were set with a target tidal volume of 6 to 8 mL/kg, FiO2: 0.40–0.45 and a respiratory rate of normocarbia. Positive end-expiratory pressure: 5 cm H2O, inspiration/expiration ratio = 1:2, and the maximum airway pressure:40 cm H2O. Hemodynamic, respiratory variables and arterial blood gases was measured, 15 minutes after induction of anesthesia in the supine position (T1), after prone position 15 minutes (T2), 30 minutes (T3), 45 minutes (T4), 60 minutes (T5), 75 minutes (T6), 90 minutes (T7).

Results:

There was no significant difference between the groups in patient characteristics. SAP, DAP, mean arterial pressure, and heart rate decreased after being placed in the prone position in all groups. Hemodynamic variables did not differ significantly between the groups. partial arterial oxygen pressure and arterial oxygen saturation levels in blood gas were found to be significantly higher in Group-PCV-VG compared to Group-PCV and Group-VCV in both the supine and prone positions. Ppeak and plateau airway pressure (Pplato) values increased and dynamic lung compliance (Cdyn) values decreased after placing the patients in the prone position in all groups. Lower Ppeak and Pplato values and higher Cdyn values were observed in both the supine and prone positions in the Group-PCV-VG group compared to the Group-PCV and Group-VCV groups.

Conclusion:

PCV-VG provides lower Ppeak and Pplato values, as well as better Cdyn, oxygenation values compared to PCV and VCV. So that PCV-VG may be an effective alternative mode of mechanical ventilation for patients in the prone position during lumbar spine surgery.
Hypoxia-derived molecular subtype and gene signature characterize prognoses and therapeutic responses in head and neck squamous cell carcinoma
Authors: Zou Jianjun , Chu Shidong , Zhou Huaien , Zhang Yiyun
Published: February 2024

Intratumoral hypoxia is widely associated with the development of malignancy, treatment resistance, and worse prognoses. This study aims to investigate the role of hypoxia-related genes (HRG) in the immune landscape, treatment response, and prognosis of head and neck squamous cell carcinoma (HNSCC). The transcriptome and clinical data of HNSCC were downloaded from TCGA and GEO databases, and HNSCC molecular subtypes were identified using non-negative matrix factorization (NMF) clustering. Prognostic models were constructed using univariate, Lasso, and multivariate Cox regression analyses. The relationship between HRGs and immune cell infiltration, immune therapy response, and drug sensitivity was evaluated, and a nomogram was constructed. 47 HRGs were differentially expressed in HNSCC, among which 10 genes were significantly associated with HNSCC prognosis. Based on these 10 genes, 2 HNSCC molecular subtypes were identified, which showed significant heterogeneity in terms of prognosis, immune infiltration, and treatment response. A total of 3280 differentially expressed genes were identified between the subtypes. After univariate, Lasso, and multivariate Cox regression analysis, 18 genes were selected to construct a novel prognostic model, which showed a significant correlation with B cells, T cells, and macrophages. Using this model, HNSCC was classified into high-risk and low-risk groups, which exhibited significant differences in terms of prognosis, immune cell infiltration, immune therapy response, and drug sensitivity. Finally, a nomogram based on this model and radiotherapy was constructed, which showed good performance in predicting HNSCC prognosis and guiding personalized treatment strategies. The decision curve analysis demonstrated its better clinical applicability compared to other strategies. HRGs can identify 2 HNSCC molecular subtypes with significant heterogeneity, and the HRG-derived risk model has the potential for prognostic prediction and guiding personalized treatment strategies.
Improving Anticoagulation Care for Pediatric Oncology Patients: A Quality Improvement Initiative
Authors: Rodriguez Vilmarie , Mitchell Brockton S. , Stanek Joseph , Vasko Katherine , Giver Jean , Monda Kay , Canini Joan , Dunn Amy A. , Kumar Riten
Published: February 2024

Background:

Cancer is associated with increased venous thromboembolism in children. Risk factors for venous thromboembolism in this cohort include using central venous catheters, mass effect from underlying malignancy, chemotherapy, and surgery. Anticoagulation management in this cohort is challenging, given recurrent episodes of thrombocytopenia, the need for invasive procedures, and coagulopathy. A quality improvement (QI) initiative was developed to improve hematology consultation services and provide documentation of an individualized anticoagulation care plan for this high-risk cohort.

Methods:

Through the use of QI methods, interviews of stakeholders, expert consensus, and review of baseline data, a multidisciplinary team was organized, and key drivers relevant to improving access to hematology consultations and documentation of individualized anticoagulation care plans were identified. We used a Plan-Do-Study-Act model to improve hematology consultations and documentation of anticoagulation care plan (process measure). Outcome measures were bleeding and thrombosis recurrence/progression.

Results:

Seventeen patients with oncologic and venous thromboembolism diagnoses were included as baseline data. Slightly over half of these patients [53% (n = 9)] had a hematology consultation, and 7 (43.8%) had documentation of an anticoagulation care plan. After implementing QI methods, all 34 patients (100%) received hematology consultations and documentation of an anticoagulation care plan, and this measure was sustained for 1 year. Bleeding and thrombosis rates were similar in the baseline and post-QI cohorts.

Conclusions:

QI interventions proved effective in sustaining access to hematology consultations and providing anticoagulation care plans for patients with concomitant improved anticoagulation plan documentation for patients.
First Italian case of Serratia ficaria infection in a woman with obstructive pancreatitis and review of the literature.

Authors: Lucchi Giulia , Gibiino Giulia , binda Cecilia , Sbrancia Monica , Coluccio Chiara , Gatti Giulia , Taddei Francesca , Sambri Vittorio , Fabbri Carlo , Cricca Monica
Published: February 2024

Introduction:  Serratia ficaria, is a Gram-negative rod first identified in 1979 in the fig tree ecosystem. Since then, Serratia ficaria has been occasionally isolated from human specimens. According to literature, Serratia ficaria is an opportunistic pathogen that rarely affects human, when infection occurs it can lead to different clinical conditions, including gallbladder empyema, lithiasis, ophthalmitis, leg ulceration, respiratory infections.
 
Case presentation: We report the case of a 66-year-old woman in whom Serratia ficaria was the causative agent of acute obstructive jaundice. The woman was treated empirically with ceftriaxone and metronidazole before sphincterotomy.Serratia ficaria was isolated from bile samples collected by Endoscopic Retrograde Cholangiopancreatography (ERCP).
 
Conclusion: Serratia ficaria causes mild infections in most cases, however, severe infections such as soft tissue infections or septicemia are reported in the literature. In this case, ERCP was crucial in the diagnosis and treatment of the patient, which favorably resolved the infection.
Exploring muscle recruitment by Bayesian methods during motion
Authors: Amankwah M , Bersani A , Calvetti D , Davico G , Somersalo E , Viceconti M
Published: February 2024

The human musculoskeletal system is characterized by redundancy in the sense that the number of muscles exceeds the number of degrees of freedom of the musculoskeletal system. In practice, this means that a given motor task can be performed by activating the muscles in infinitely many different ways. This redundancy is important for the functionality of the system under changing external or internal conditions, including different diseased states. A central problem in biomechanics is how, and based on which principles, the complex of central nervous system and musculoskeletal system selects the normal activation patterns, and how the patterns change under various abnormal conditions including neurodegenerative diseases and aging. This work lays the mathematical foundation for a formalism to address the question, based on Bayesian probabilistic modeling of the musculoskeletal system. Lagrangian dynamics is used to translate observations of the movement of a subject performing a task into a time series of equilibria which constitute the likelihood model. Different prior models corresponding to biologically motivated assumptions about the muscle dynamics and control are introduced. The posterior distributions of muscle activations are derived and explored by using Markov chain Monte Carlo (MCMC) sampling techniques. The different priors can be analyzed by comparing the model predictions with actual observations.
Circadian period is compensated for repressor protein turnover rates in single cells
Authors: Gabriel Christian H. , del Olmo Marta , Widini Arunya Rizki , Roshanbin Rashin , Woyde Jonas , Hamza Ebrahim , Gutu Nica-Nicoleta , Zehtabian Amin , Ewers Helge , Granada Adrian , Herzel Hanspeter , Kramer Achim
Published: February 2024

Most mammalian cells possess molecular circadian clocks generating widespread rhythms, e.g. in transcript and protein abundance. While circadian clocks are robust to fluctuations in the cellular environment, little is known about how circadian period is compensated for fluctuating metabolic states. Here, we exploit the heterogeneity of single cells both in circadian period and metabolic state, governing protein stability, to study their interdependence without the need for genetic manipulation. We generated cells expressing key circadian proteins (CRY1/2 and PER1/2) as endogenous fusions with fluorescent proteins and simultaneously monitored circadian rhythms and degradation in thousands of single cells. We found that the circadian period is compensated for fluctuations in the turnover rates of circadian repressor proteins and uncovered possible mechanisms using a mathematical model. In addition, the stabilities of the repressor proteins are circadian phase-dependent and correlate with the circadian period in a phase-dependent manner, in contrast to the prevailing model.
Bigtools: a high-performance BigWig and BigBed library in Rust
Authors: Huey Jack D. , Abdennur Nezar
Published: February 2024

The BigWig and BigBed file formats were originally designed for the visualization of next-generation sequencing data through a genome browser. Due to their versatility, these formats have long since become ubiquitous for the storage of processed sequencing data and regularly serve as the basis for downstream data analysis. As the number and size of sequencing experiments continues to accelerate, there is an increasing demand to efficiently generate and query BigWig and BigBed files in a scalable and robust manner, and to efficiently integrate these functionalities into data analysis environments and third-party applications. Here, we presentBigtools, a feature-complete, high-performance, and integrable software library for generating and querying both BigWig and BigBed files.Bigtoolsis written in the Rust programming language and includes a flexible suite of command line tools as well as bindings to Python.Bigtoolsis cross-platform and released under the MIT license. It is distributed on Crates.io and the Python Package Index, and the source code is available athttps://github.com/jackh726/bigtools.
A learnable transition from low temperature to high temperature proteins with neural machine translation
Authors: Komp Evan , Phillips Christian , Alanzi Humood N. , Zorman Marlo , Beck David A. C.
Published: February 2024

This work presents Neural Optimization for Melting-temperature Enabled by Leveraging Translation (NOMELT), a novel approach for designing and ranking high-temperature stable proteins using neural machine translation. The model, trained on over 4 million protein homologous pairs from organisms adapted to different temperatures, demonstrates promising capability in targeting thermal stability. A designed variant of theDrosophila melanogasterEngrailed Homeodomain shows increased stability at high temperatures, as validated by estimators and molecular dynamics simulations. Furthermore, NOMELT achieves zero-shot predictive capabilities in ranking experimental melting and half-activation temperatures across two protein families. It achieves this without requiring extensive homology data or massive training datasets as do existing zero-shot predictors by specifically learning thermophilicity, as opposed to all natural variation. These findings underscore the potential of leveraging organismal growth temperatures in context-dependent design of proteins for enhanced thermal stability.
Evaluation of melanocyte stem cell population in vitiliginous skin pre- and post-narrow-band UVB phototherapy
Authors: Dutta Abhik , Saha Dyuti , Poojary Manish , Nagesh T S , Jamora Colin
Published: February 2024

Vitiligo vulgaris is an autoimmune disorder characterized by the destruction of epidermal melanocytes leading to white lesions devoid of pigmentation. The destruction of epidermal melanocytes. Is driven by tissue-resident and circulatory immune cells that maintain an inflammatory milieu. Two percent of the global population suffer from vitiligo vulgaris, of which, prevalence is higher in the Indian population. Narrow-band UV-B (NBUVB) phototherapy is commonly used as an economical, non-invasive, and well-tolerated treatment modality. NBUVB promotes the migration of melanocyte stem cells (MelSC) to the epidermis, thus regaining pigmentation in affected individuals.

Despite the widespread use of NBUVB in secondary and tertiary clinics in India, the status of melanocyte stem cells and immune cells, pre-and post-NBUVB is not well understood. We observe that following NBUVB phototherapy, melanocyte stem cells (pax3+) re-populate the epidermis and express melanogenesis markers (Tyrosinase, Trp2, kit) concomitant with a decrease in CD3+ T-cells within the skin. Our study reaffirms the therapeutic efficacy of NBUVB in promoting re-pigmentation in an Indian cohort of vitiligo patients. Further, NBUVB is effective in reducing overall immune load, widely considered a major contributor to the pathogenesis of the disease.
A lack of open data standards for large infrastructure project hampers social-ecological research in the Brazilian Amazon
Authors: Hyde J.L. , Swanson A.C. , Bohlman S.A. , Athayde S. , Bruna E.M. , Valle D.R.
Published: February 2024

New infrastructure projects are planned or under construction in several countries, including in the bioculturally diverse Amazon, Mekong, and Congo regions. While infrastructure development can improve human health and living standards, it may also lead to environmental degradation and social change. Accessible, high quality data about infrastructure projects is essential for both monitoring them and studying their social and environmental impacts. We investigated the availability and quality of data on infrastructure projects in the Brazilian Amazon by reviewing the academic literature and surveying researchers from the conservation and development community, then used the results of these surveys to identify critical data attributes for the gathering, organizing, and sharing of infrastructure data by social-ecological researchers and practitioners.

Although data on infrastructure in the Brazilian Amazon were generally available, they were often of poor quality and lacked information critical for monitoring and research. Data were often difficult to find and reformat, resulting in loss of time and resources for researchers and other stakeholders. Discrepancies between researchers’ survey responses on data needs and the types of data used in peer-reviewed articles on infrastructure projects indicate the following information was often missing: geographic extent of the project, construction and operation dates, and project type (e.g., paved vs unpaved road). Including these data in a standardized format, along with making them more readily accessible by hosting them in public repositories and ensuring they are current and comprehensive, would facilitate research and improve planning, decision-making, and monitoring of existing and future infrastructure projects in Brazil and other developing countries.

Highlights

Infrastructure projects across the globe spur economic development but also lead to social- ecological degradation.

Researchers and practitioners need current and comprehensive data to better mitigate social- ecological changes from infrastructure.

Infrastructure data are often unavailable, inaccessible, or incomplete.

Finding and organizing datasets cost researchers hundreds of hours and may lead to abandoned projects.

To promote better research outcomes, governments and NGOs should ensure datasets on infrastructure are accessible, current, comprehensive, and include such vital information as the project’s geographic extent, dates of construction and operation, project type, and essential technical data.
1.4 min Plasma Proteome Profiling via Nanoparticle Protein Corona and Direct Infusion Mass Spectrometry
Authors: Jiang Yuming , Meyer Jesse G.
Published: February 2024

Non-invasive detection of protein biomarkers in plasma is crucial for clinical purposes. Liquid chromatography mass spectrometry (LC-MS) is the gold standard technique for plasma proteome analysis, but despite recent advances, it remains limited by throughput, cost, and coverage. Here, we introduce a new hybrid method, which integrates direct infusion shotgun proteome analysis (DISPA) with nanoparticle (NP) protein coronas enrichment for high throughput and efficient plasma proteomic profiling. We realized over 280 protein identifications in 1.4 minutes collection time, which enables a potential throughput of approximately 1,000 samples daily. The identified proteins are involved in valuable pathways and 44 of the proteins are FDA approved biomarkers. The robustness and quantitative accuracy of this method were evaluated across multiple NPs and concentrations with a mean coefficient of variation at 17%. Moreover, different protein corona profiles were observed among various nanoparticles based on their distinct surface modifications, and all NP protein profiles exhibited deeper coverage and better quantification than neat plasma. Our streamlined workflow merges coverage and throughput with precise quantification, leveraging both DISPA and NP protein corona enrichments. This underscores the significant potential of DISPA when paired with NP sample preparation techniques for plasma proteome studies.
Time-varying mediation analysis for incomplete data with application to DNA methylation study for PTSD
Authors: Wei Kecheng , Xue Fei , Xu Qi , Yuan Yubai , Zhang Yuexia , Qin Guoyou , Wani Agaz H. , Aiello Allison E. , Wildman Derek E. , Uddin Monica , Qu Annie
Published: February 2024

DNA methylation (DNAm) has been shown to mediate causal effects from traumatic experiences to post-traumatic stress disorder (PTSD). However, the scientific question about whether the mediation effect changes over time remains unclear. In this paper, we develop time-varying structural equation models to identify cytosine-phosphate-guanine (CpG) sites where DNAm mediates the effect of trauma exposure on PTSD, and to capture dynamic changes in mediation effects. The proposed methodology is motivated by the Detroit Neighborhood Health Study (DNHS) with high-dimensional and longitudinal DNAm measurements. To handle the non-monotone missing DNAm in the dataset, we propose a novel Longitudinal Multiple Imputation (LMI) method utilizing dependency among repeated measurements, and employ the generalized method of moments to integrate the multiple imputations. Simulations confirm that the proposed method outperforms existing approaches in various longitudinal settings. In DNHS data analysis, our method identifies several CpG sites where DNAm exhibits dynamic mediation effects. Some of the corresponding genes have been shown to be associated with PTSD in the existing literature, and our findings on their time-varying effects could deepen the understanding of the mediation role of DNAm on the causal path from trauma exposure to PTSD risk.
Small LEA proteins as an effective air-water interface protectant for fragile samples during cryo-EM grid plunge freezing
Authors: Abe Kaitlyn M. , Lim Ci Ji
Published: February 2024

Sample loss due to air-water interface (AWI) interactions is a significant challenge during cryo-electron microscopy (cryo-EM) sample grid plunge freezing. We report that small Late Embryogenesis Abundant (LEA) proteins, which naturally bind to AWI, can protect samples from AWI damage during plunge freezing. This protection is demonstrated with two LEA proteins from nematodes and tardigrades, which rescued the cryo-EM structural determination outcome of two fragile multisubunit protein complexes.
RNA Splicing Junction Landscape Reveals Abundant Tumor-Specific Transcripts in Human Cancer
Authors: Li Qin , Li Ziteng , Chen Bing , Zhao Jingjing , Yu Hongwu , Hu Jia , Lai Hongyan , Zhang Hena , Li Yan , Meng Zhiqiang , Hu Zhixiang , Huang Shenglin
Published: February 2024

RNA splicing is a critical process governing gene expression and transcriptomic diversity. Despite its importance, a detailed examination of transcript variation at the splicing junction level remains scarce. Here, we perform a thorough analysis of RNA splicing junctions in 34,775 samples across multiple sample types. We identified 29,051 tumor-specific transcripts (TSTs) in pan-cancer, with a majority of these TSTs being unannotated. Our findings show that TSTs are positively correlated with tumor stemness and linked to unfavorable outcomes in cancer patients. Additionally, TSTs display mutual exclusivity with somatic mutations and are overrepresented in transposable element-derived transcripts possessing oncogenic functions. Importantly, TSTs can generate neoepitopes that bind to MHC class I molecules for immunotherapy. Moreover, TSTs can be detected in blood extracellular vesicles from cancer patients. Our results shed light on the intricacies of RNA splicing and offer promising avenues for cancer diagnosis and therapy.

In brief

This study thoroughly analyzed RNA splicing junctions in 34,775 samples and identified 29,051 tumor-specific transcripts (TSTs), which may serve as novel cancer driver genes, neoantigens, and circulating biomarkers.

Graphical abstract
Granulosa cell-layer stiffening prevents the granulosa cells from escaping the post-ovulatory follicle
Authors: Wang Xiaodong , Liao Jianning , Shi Hongru , Zhao Yongheng , Ke Wenkai , Wu Hao , Liu Guoshi , Li Xiang , He Changjiu
Published: February 2024

Ovulation is necessary for successful reproduction. After ovulation, cumulus cells and oocytes are released, while granulosa cells (GCs) remain trapped within the post-ovulatory follicle to form the corpus luteum. However, the mechanism underlying GC confinement has long been unclear. Here, we providein vitroandin vivoevidence demonstrating that the stiffening of GC-layer as an evolutionarily conserved mechanism that hinders GCs from escaping the post-ovulatory follicles. Spatial transcriptome analysis reveals that the assembly of focal adhesions is primarily responsible for this stiffening. Disrupting focal adhesion assembly through RNA interference results in the release of GCs from the post-ovulatory follicle, leading to the formation of an aberrant corpus luteum with reduced cell density and cavities. We also uncover that theLH (hCG) -cAMP-PKA-CREBsignaling axis stimulates focal adhesion assembly and induce GC-layer stiffening. Our findings introduce a novel concept of “GC-layer stiffening”, which offers valuable insights into the factors that prevent GCs escape from the post-ovulatory follicle.
The interplay between proton diffusion across biological membranes and their biophysical properties highlights the role of defects in mixed lipid membranes
Authors: Variyam Ambili Ramanthrikkovil , Rzycki Mateusz , Yucknovsky Anna , Stuchebrukhov Alexei A. , Drabik Dominik , Amdursky Nadav
Published: February 2024

Proton circuits within biological membranes are at the heart of natural bioenergetic systems, whereas different biological membranes are characterized by different lipid compositions. In this study, we investigate how the composition of mixed lipid membranes influences the proton transfer (PT) properties of the membrane by following the excited-state PT (ESPT) process from a tethered probe to the membrane with time-scales and length-scales of PT that are relevant to bioenergetic systems. Two processes can happen during ESPT: the initial PT from the probe to the membrane at short timescales, followed by diffusion of dissociated protons around the probe on the membrane, and the possible geminate recombination with the probe at longer timescales. Here, we use membranes that are composed of mixtures of phosphatidylcholine (PC) and phosphatidic acid (PA). We show that the changes in the ESPT properties are not monotonous with the concentration of the lipid mixture; at low concentration of PA in PC, we find that the membrane is a poor proton acceptor. Molecular dynamics simulations indicate that at this certain lipid mixture, the membrane has the least defects (more structured and unflawed). Accordingly, we suggest that defects can be an important factor in facilitating PT. We further show that the composition of the membrane affects the geminate proton diffusion around the probe, whereas, on a time-scale of tens of nanoseconds, the dissociated proton is mostly lateral restricted to the membrane plane in PA membranes, while in PC, the diffusion is less restricted by the membrane.
Surface adhesion and membrane fluctuations influence the elastic modulus of extracellular vesicles
Authors: Stridfeldt Fredrik , Kylhammar Hanna , Metem Prattakorn , Pandey Vikash , Agrawal Vipin , Görgens Andre , Mamand Doste R. , Gustafsson Oskar , El Andaloussi Samir , Mitra Dhrubaditya , Dev Apurba
Published: February 2024

Elastic properties of nanoscale extracellular vesicles (EVs) are believed to influence their cellular interactions, thus having a profound implication in intercellular communication. Yet, an accurate quantification of the elasticity of such small lipid vesicles is difficult even with AFM-based nanoindentation experiments as it crucially depends on the reliability of the theoretical interpretation of such measurements. Here we describe a complete method composed of theoretical framework, experimental procedure, and appropriate statistical approach for an accurate determination of bending modulus and effective elastic modulus of EVs. Further, we experimentally demonstrate that the quantification of EVs by the elastic modulus from AFM-based force spectroscopy measurement is marred by the interplay of their compositionally inhomogeneous fluid membrane with the adhesion forces from the substrate and thermal effects - two exquisite phenomena that could thus far only be theoretically predicted. The effects result in a large spreading of elastic modulus even for a single EV. Our unified model is then applied to genetically engineered classes of EVs to understand how the alterations in tetraspanin expression may influence their elastic modulus.