bluuebunny/crossref_metadata_2025 huggingface dataset:
3D multiscale characterization of the human placenta: Bridging anatomy and histology by X-ray phase-contrast tomography
Authors: Reichmann Jakob , Schnurpfeil Anne , Mittelstädt Sylvia , Jensen Patrick Moller , Dahl Vedrana Andersen , Dahl Anders Bjorholm , Weide Carina , von Campenhausen Eva , Dejea Hector , Tafforeau Paul , Werlein Christopher , Jonigk Danny , Ackermann Maximilian , Engel Klaus , Gallwas Julia , Dietz Alexander , Hasanov Mir Fuad , Salditt Tim
Published: January 2025

The human placenta exhibits a complex three-dimensional (3D) structure with a interpenetrating vascular tree and large internal interfacial area. In a unique and yet insufficiently explored way, this parenchymal structure enables its multiple functions as a respiratory, renal, and gastrointestinal multiorgan. The histopathological states are highly correlated with complications and health issues of mother, and fetus or newborn. Macroscopic and microscopic examination has so far been challenging to reconcile on the entire organ. Here we show that anatomical and histological scales can be bridged with the advent of hierarchical phase-contrast tomography and highly brilliant synchrotron radiation. To this end, we are exploiting the new capabilities offered by the BM18 beamline at ESRF, Grenoble for whole organ as well as the coherence beamline P10 at DESY, Hamburg for high-resolution, creating unique multiscale datasets. We also show that within certain limits, translation to μCT instrumentation for 3D placenta examination becomes possible based on advanced preparation and CT protocols, while segmentation of the datasets by machine learning now remains the biggest challenge.
Towards faster quality control of personal radiation protective equipment using CT scout or a dedicated biplanar radiography device
Authors: Kellens Pieter-Jan , Bayart Sandrine , De Pooter Jan , Bacher Klaus
Published: January 2025

Quality control (QC) of personal radiation protective equipment (PRPE) is essential to detect tears and holes in the attenuating layers. Routinely, this QC is performed using fluoroscopy on a conventional X-ray table. However, such a QC procedure is laborious and time consuming. This study aims to establish faster PRPE QC using CT scout or a biplanar radiography device. A reproducible 0.25 mm lead-equivalent phantom of ten holes (diameter 10 mm – 1 mm) and two incisions (length 50 mm and 25 mm with a width of 0.63 mm) was created to assess the defect detection performance using fluoroscopy, CT scout (Siemens Somatom Definition Flash and GE Revolution) and a biplanar radiography device (EOS). Additionally, three pieces of PRPE were imaged on all modalities and compared in terms of speed and defect detection performance. Defect quantification was performed with an X-ray opaque grid, the modality’s line tool and the built-in wand tool in ImageJ software. All modalities could visualize the smallest defects (1 mm). However, for the Siemens Flash, the smallest defect was only visible when the scout length was at most 50 cm. Fluoroscopy was the most time consuming (>1 min/piece). Both CT scout and the EOS allowed faster analysis (<10 s). The EOS system had the highest resolution of 5.19 pixels/mm for all set scan speeds. However, to image the reference pieces, a seamstress doll was needed. The wand tool was found to be the most accurate for defect estimation. Both the EOS and a CT scout allowed faster QC of PRPE with equivalent defect detection performance. However, specific positioning and scan length must be considered.
Taxonomic revision of Chilean Liogenys (Coleoptera: Melolonthidae) and molecular assessment of a species complex
Authors: Cherman Mariana A , Basílio Daniel S , Clarkson Bruno , Mondaca José , Bezděk Aleš , Smith Andrew B T , Almeida Lúcia M
Published: January 2025

Liogenys is a neotropical genus widely distributed in South America and characterized by rhizophagous feeding habits. Taxonomy survey of Liogenys from Chile revealed a species complex consisting of L. palpalis, L. obesula and an undescribed morphotype. Morphological data alone are not sufficient to distinguish between them. The three-species hypothesis was tested using phylogenetic and preliminary phylogeographic analyses, as well as unilocus delimitation methods using mitochondrial (COI) and nuclear (ITS2) markers. The tree-based PTP method based on ITS2 considers both L. obesula and the undescribed morphotype to be variants of L. palpalis, a single, polymorphic species. Haplotypes from 12 localities along central Chile revealed four genetically structured populations, with statistical variance (54.34%) only within them. Isolated populations occur in Southern Santiagan Region and coastal desert. There are eight species of Liogenys in Chile. Diagnoses are provided for five species. Liogenys elguetai sp. nov. is described. Five synonyms are proposed for three species. Liogenys pubisternis, a new synonym of L. palpalis, is transferred from Diplotaxis. Lectotypes are provided for four names (L. castaneus, L. grandis, L. pubisternis, and Melolontha palpalis). Liogenys boliviensis is recorded for the first time from Chile and Peru, extending the distribution of Liogenys to northernmost Chile.
Biglycan stimulates retinal pathological angiogenesis via up‐regulation of CXCL12 expression in pericytes
Authors: Liu Miaomiao , Zhao Peiquan , Feng Huazhang , Yang Yuan , Zhang Xuerui , Chen Enguang , Xiao Haodong , Luo Jia , Chen Han , Yin Jiawei , Lin Min , Mao Ruixue , Zhu Xingping , Li Jing , Fei Ping
Published: January 2025

Retinal pathological angiogenesis (PA) is a common hallmark in proliferative retinopathies, including age‐related macular degeneration (AMD), proliferative diabetic retinopathy (PDR), and retinopathy of prematurity (ROP). The mechanisms underlying PA is complex and incompletely understood. In this study, we investigated the role of extracellular matrix (ECM) protein biglycan (BGN) in PA using an oxygen‐induced retinopathy (OIR) mouse model, along with hypoxia (1% O2) conditions for incubating pericytes and endothelial cells in vitro. We found a significant upregulation of Bgn in the retinas of OIR mice. Intravitreal injection of Bgn‐specific small interfering RNA (siRNA) in OIR mice at postnatal day 12 (P12) effectively curbed retinal PA at P17. Using cultured cells, we found that BGN expression in pericytes was highly sensitive to hypoxic stimulation compared to endothelial cells. We further showed that BGN stimulated retinal PA via the upregulation of C‐X‐C motif chemokine ligand 12 (CXCL12). Inhibition of the CXCL12‐CXCR4 axis effectively diminished PA in OIR mouse. In conclusion, our study demonstrated the stimulatory role of BGN in retinal PA, identified the link between BGN and CXCL12 expression, and further highlighted the role of pericytes in retinal PA.
Revision Triceps Reconstruction With Achilles Bone Block Allograft Augmentation: A Novel Inlay Technique
Authors: Weber Matthew B. , Lee Glenn , Cotterell Ilvy
Published: January 2025

Managing rerupture of the triceps brachii tendon after surgical repair is challenging due to poor tissue quality, retraction, and adhesions. This clinical scenario often requires augmentation with native tissue or tendon allografts. Traditional techniques include V-Y advancement, reinforced triceps advancement with double row or suture bridge fixation, and allograft tendon augmentation. This paper presents a novel method of fixation using an Achilles tendon allograft with a calcaneal bone block which aims to enhance previously described techniques. This new technique involves inserting an Achilles allograft calcaneal bone plug into the dorsal ulna to increase surface area for primary bone healing. The bone plug is then secured under a precontoured locking plate, potentially reducing the risks of displacement or fixation failure. This also avoids the placement of screws through the calcaneal plug, which puts it at risk for fracture. This technique also has drawbacks, such as increased costs, the potential need for a second surgery to remove hardware, and more extensive soft tissue dissection. In the patient case described, this method effectively reconstructed the triceps tendon in a revision setting.
Mini-boomerang Approach for the Treatment of Specific Laterally-based Fracture Patterns of the Glenoid and Scapular Neck
Authors: LaRoque Michael C. , Pedri Tony G. , Brahme Indraneel S. , Cole Peter A.
Published: January 2025

Background:

Several posterior approaches have been developed for scapula neck and body fractures undergoing operative management, with variations balancing priorities of visualization and minimization of soft tissue disruption. Seldom, consideration is given to adjusting the surgical approach based on specific and known fracture patterns. The purpose of this manuscript is to describe the mini-boomerang surgical technique for surgeons encountering a subtype of less common fracture patterns and report clinical outcomes for 7 patients after surgical treatment with this approach.

Methods:

For a subtype of laterally-based scapula fractures isolated to the scapular anatomic neck ± glenoid, and/or crossing the scapular spine, we describe and illustrate the mini-boomerang, a variation on the classic Judet incision. This cohort included 4 men and 3 women with a mean age of 39 years (range = 23 to 57). Postoperatively, all patient scores for disabilities of shoulder and hand (DASH), along with a range of motion and strength measurements for the injured and contralateral shoulder, were collected.

Results:

Seven patients underwent mini-boomerang incision for scapula fractures. Five patients achieved follow-up of 12 months or greater (mean= 24; range=14 to 31 months). The mean ROM for the injured versus uninjured shoulder at final follow-up was 99% for forward flexion (FF), 98% for abduction (ABD), and 75% for external rotation (ER). The mean postoperative strength of the injured versus uninjured shoulder at final follow-up was 81% for FF, 92% for ABD, and 70% for ER.

Conclusion:

The mini-boomerang approach decreases soft tissue exposure while enhancing visualization for fracture reduction and fixation.
Comparison of Predictable Ability Measure Using Examinations and Nursing Licensure Success
Authors: Terry Stephanie , Chery Sheila , Viger Steven G. , Moran Vicki , Madden Sara , Rightler Kayla
Published: January 2025

End-of-program predictive examinations have been in existence in nursing education for over 10 years. Nursing schools have used these examinations to prepare students on the testable content from National Council of State Boards of Nursing (NCSBN), which has been delivering the NCLEX-RN since 1994. Nursing students, in the final semester of the nursing program, took the Predictable Ability Measurement Readiness (PAMR) 1 and/or 2. The 100-question exam was developed by nursing subject matter experts following the 2019 NCLEX-RN blueprint content, item types, and scoring. The PAMR scores were examined and compared with the results of the nursing students on the NCLEX-RN. Statistical analysis revealed that the students who passed the NCLEX-RN on their first attempt had higher scores on the PAMR1. A cut-point scale using regression modeling was developed to determine a minimal score compared with the probability of passing NCLEX-RN. Nursing faculty have a reliable and predictable exam to use to prepare students to take the NCLEX-RN. The PAMR 1 and 2 have demonstrated the ability to predict passing on the NCLEX-RN and can be used confidently in nursing programs for licensure examination preparation.
Radiofrequency Microneedling in Treating Primary Hyperhidrosis: A Systematic Review and Meta-Analysis
Authors: Vaish Mayuri H. , Hadeler Edward , Guda Anisha , Goff Heather
Published: January 2025

BACKGROUND

Radiofrequency microneedling (RFM) is a potential treatment for primary hyperhidrosis. However, its efficacy is unclear, and treatment parameters and outcomes vary across studies.

OBJECTIVE

To understand the effect of RFM on treating primary hyperhidrosis, as measured by changes in the Hyperhidrosis Disease Severity Score (HDSS) before and after treatment, and to clearly define treatment settings most likely to optimize results.

MATERIALS AND METHODS

A systematic literature search utilizing Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted across PubMed, EMBASE, MEDLINE, Web of Science, and the Cochrane Library. Studies were evaluated for risk of bias via the ROBINS-I tool and Levels of Evidence/GRADE criteria. A random forest model identified RFM settings that predict HDSS score decrease.

RESULTS

Six publications met inclusion criteria. The level of evidence was classified as Grade B, indicating moderate quality. RFM intervention resulted in a mean HDSS score decrease of 1.63 (52% reduction, p < .05). The strongest predictors for HDSS score decrease were dwell time, energy, and depth, with feature importances of 0.43, 0.19, and 0.15 respectively.

CONCLUSION

Radiofrequency microneedling treatment significantly reduces HDSS scores in patients with primary hyperhidrosis. Moving forward, it would benefit physicians to standardize objective protocols in reporting RFM parameters and measuring outcomes.
Clinical outcomes of best practices for the treatment of distal ulcerative colitis
Authors: Okeke Nzubechukwu G. , Omeludike Eunice K. , Aregbesola Eunice T. , Elendu Chukwuka , Obidigbo Babajide T. , Oshobu Ibukunoluwa E. , Beeko Papa K.A. , Adenuga Ebunoluwa G. , Sowunmi Oreoluwa A. , Adetoye Stephen D. , Mensah Linda S. , Adetoye Richard O.
Published: January 2025

Distal ulcerative colitis (DUC), affecting 30–50% of ulcerative colitis (UC) patients, is a subtype characterized by inflammation limited to the rectum and sigmoid colon. The pathogenesis involves a complex interplay of genetic, environmental, and immune factors, with cytokines like TNF-α, IL-1β, IL-6, and IL-17 playing significant roles. Despite therapeutic advancements, distal ulcerative colitis presents unique challenges due to its localized nature and diverse response to treatments. This review examined 50 randomized controlled trials (RCTs) that explored pharmacological and non-pharmacological interventions for distal ulcerative colitis, focusing on symptom remission, mucosal healing, and quality-of-life outcomes. Key findings revealed that pharmacologic treatments, particularly 5-aminosalicylic acid (5-ASA), corticosteroids, and biologics, effectively achieved remission, with combined therapies beneficial in refractory cases. Non-pharmacologic strategies, including lifestyle modifications and patient education, further supported treatment efficacy by enhancing patient adherence and outcomes. Importantly, trials highlighted that individualized approaches – such as early biologic therapy for patients with moderate-to-severe disease, dose adjustments based on patient demographics, and tailored lifestyle recommendations – enhanced treatment response and patient quality of life. The review underscores the necessity of personalized management strategies that integrate these findings to address distal ulcerative colitis’s heterogeneous nature and improve long-term patient outcomes.
Evaluation of Gamma Index Analysis for Detecting Errors in Patient-specific Quality Assurance in Intensity Modulated Radiotherapy
Authors: Tuğrul Taylan
Published: January 2025

Quality assurance practices performed before treatment are believed to identify various potential errors. In this study, 2-dimensional (2D) dosimetric results were analyzed by making some intentional mistakes in six different treatment plans. In this way, the detectability of errors was investigated. In all segments of all treatment plans, one of the multileaf collimators was kept fixed at different positions on the central axis. In addition to multileaf collimators error, gantry error was also examined in the study. The dose distribution results obtained by Treatment Planning System (TPS) were compared with those obtained by the 2D array device, both as local calculation and global calculation methods, using the gamma analysis method. When the results are examined in the case where the Multi-leaf collimators (MLC) is fixed at the 1 cm position, the gamma analysis pass rate of the other plans, except two plans in the MD criterion, are calculated above the 95% limit. When the dose distributions obtained as a result of irradiation with 0.5-degree erroneous gantry angle were analyzed, it was found that all plans were at an acceptable rate in the maximum dose criterion. In case of incorrect irradiation, dose reduction or overdose may occur in the irradiated target area, even if gamma analysis pass rates are sufficient. Quality control procedures performed before treatment may be less effective. It is suggested that it would be better to examine the gamma analysis criteria applied for error detection with different values and local calculation method, and that device-based quality controls should be performed frequently.
“Central retinal artery occlusion following scleral buckling surgery with gas insertion in a patient with sickle cell disease”
Authors: Jalil Assad , Lippera Myrta , Ivanova Tsveta
Published: January 2025

Purpose-

To describe a case of central retinal artery occlusion following scleral buckling procedure combined with pneumoretinopexy in a patient with sickle cell (HbSC) retinopathy (SCR).

Methods-

Scleral buckling procedure, combined with injection of 0.3 ml of 100% perfluoropropane (C3F8) gas in the vitreous, was performed without intra-operative complications under general anaesthesia as treatment of two separate macula-sparing rhegmatogenous retinal detachments secondary to round holes, involving superior and inferior retina respectively, in the right eye of a 26-year-old Afro-Caribbean female with sickle cell disease.

Results-

On day one post-operatively, central retinal artery occlusion (CRAO) was detected in the operated eye. We hypothesize that the expansion of the gas in the postoperative period combined with the presence of a retinal explant might have caused a moderate elevation of the IOP that caused extensive retinal arteriolar shutdown in the backdrop of SCR.

Conclusion-

CRAO can be a devastating complication following scleral buckling procedure combined with gas insertion in SCR, caution is required when performing scleral explant combined with expansile gas in a patient with sickle cell vasculopathy.
MRSA Cellulitis with Orbital and Retinal Abscesses Resulting in Lemierre Syndrome Following Eyebrow Piercing
Authors: Erb Bethany M. , Jeffrey Joseph H. , Reed Donovan S. , Hobbs Samuel D. , Brundridge Wesley L.
Published: January 2025

We describe a case of orbital cellulitis with abscess formation following eyebrow piercing complicated by internal jugular vein thrombosis and subretinal abscesses requiring enucleation with orbital abscess drainage. The popularity of body piercing is increasing and physicians should be familiar with the possibility and management of vision-threatening complications of facial piercing. Following left eyebrow piercing, a 20-year-old female experienced increasing periorbital swelling, erythema, chemosis, orbital pain, decreased vision, and concomitant fever, chills, and rhinorrhea. She was found to have left orbital cellulitis with multiple orbital abscesses, intracranial thromboses, internal jugular vein thrombosis, and septic pulmonary emboli consistent with Lemierre syndrome. Treatment of her condition included broad-spectrum intravenous antibiotics, anticoagulation, orbital abscess drainage, and ultimately OS enucleation. To the authors’ knowledge, this is the first case of orbital infection and Lemierre syndrome following eyebrow piercing.
Medication Withdrawal With Normal or Near-normal Histology in Ulcerative Colitis is Associated With Clinical Relapse
Authors: Shaffer Seth R. , Chu Jenny , Algarni Amal , Nugent Zoann , Schaeffer David F. , Bernstein Charles N.
Published: January 2025

Goals:

We sought to understand the clinical course and risk of dysplasia in persons with UC who achieve near or complete normalization of histology.

Background:

Histologic remission and normalization in ulcerative colitis (UC) is associated with improved clinical outcomes. We sought to understand the clinical course and risk of dysplasia in persons with UC who achieve near or complete normalization of histology.

Study:

We performed a retrospective single-centred study of persons with UC who were in endoscopic remission with normal histology. Pathology slides were reread by a gastrointestinal-expert pathologist and both right and left colon were scored using the Geboes score. The primary outcome was time to clinical relapse, with secondary outcomes including episodes of dysplasia and colectomy.

Results:

Seventy-eight persons had normal histology reported, although only 2 had completely normal histology on expert review. Approximately one-fifth of persons developed a clinical relapse at a mean of 4.7 years. Neither right nor left-sided colon histology was predictive of future clinical relapse. Forty-three percent of those who withdrew their IBD-therapy had a future clinical relapse, and were more likely to relapse than those who did not withdraw therapy (HR: 4.89, 95% CI: 1.32-18.08). There were zero episodes of dysplasia in follow-up, and 2 persons who relapsed ended up receiving a colectomy.

Conclusions:

Persons with UC who achieve normal or near-normal histology have moderate rates of clinical relapse. Physicians should be cautious when considering withdrawing IBD-therapy as this was associated with an increased risk of clinical relapse.
Gut-brain Axis and Irritable Bowel Syndrome During the Lockdown due to the SARS-CoV-2 Pandemic
Authors: Piskorz María Marta , Stefanolo Juan Pablo , Ibañez Agustin , Eugenia Hesse , Bravo Velez Gladys , Tevez Adriana , Gutierrez Cielo , Uehara Tatiana , Hashimoto Harumi , Puga-Tejada Miguel , Gonzalez Ballerga Esteban , Olmos Jorge Atilio
Published: January 2025

Background:

Irritable bowel syndrome (IBS) is influenced by various factors, including socioemotional stressors. The COVID-19 lockdown created a unique environment characterized by reduced social interactions, potentially impacting IBS symptoms.

Aim:

To assess how lockdown measures affected symptoms related to the gut-brain axis in IBS patients in Buenos Aires, Argentina.

Methods:

Patients with IBS-diarrhea subtype who previously participated in surveys were re-surveyed during the lockdown. Surveys included symptom severity scales and assessments for anxiety, depression, and somatization.

Findings:

One hundred twenty-nine patients (median age 57 y, 78% female) were surveyed. Severe IBS decreased (40.4% vs. 25%; P<0.001), along with abdominal discomfort (72.4% vs. 43%; P<0.001), bloating (72.4% vs. 51.5%; P<0.001), and Bristol scale (6 vs. 4; P<0.001) during-lockdown. Headache and dyspepsia increased, whereas anxiety (45.8% vs. 34.9%; P=0.014) and severe somatization (29.6% vs. 23.3%; P=0.081) decreased.

Conclusion:

Lockdown was associated with improved clinical status in IBS-D patients, reflected in reduced somatization, anxiety, and symptom intensity. This may be attributed to decreased exposure to external stressors on the gut-brain axis.
Navigating Bowel Preparation for Colonoscopy
Authors: Hagen Rachael , Nguyen Minh Thu T. , Anderson Joseph C. , Birk John W.
Published: January 2025

Colorectal cancer (CRC) is the third most common cancer in the United States. Early detection through colonoscopy significantly improves survival rates. Detecting colon polyps depends on the quality of bowel preparation. However, inadequate bowel preparation remains a significant issue in clinical practice. Efforts to address this challenge have led to the development of bowel preparation regimens emphasizing efficacy, tolerability, and safety. Bowel preparation options can be categorized by their osmotic and volume properties. Isosmotic solutions based on polyethylene glycol-electrolyte lavage solutions (PEG-ELS) are available in both low-volume PEG-ELS with ascorbic acid (PEG-Asc) (e.g., MoviPrep, PLENVU) and high-volume formulations (e.g., GoLYTELY, CoLyte), as well as sulfate-free high-volume PEG-ELS formulations (SF-PEG-ELS). Hyperosmotic solutions include oral sulfate solution (OSS) (e.g., SUPREP), sodium phosphate tablets (NaP) (e.g., OsmoPrep), oral sulfate tablets (OST) (e.g., SUTAB), flavored PEG with sulfate salts (FPSS) (e.g., SUFLAVE), and magnesium citrate. Hypoosmotic solutions consist of PEG-sports drink (PEG-SD). In addition, combination solutions are available, such as sodium picosulfate with magnesium citrate (SPMC) with laxatives (e.g., CLENPIQ), and OSS with SF-PEG-ELS (Suclear). Each regimen differs in terms of cost, volume, taste, contraindications, and potential adverse effects. Therefore, clinicians must carefully evaluate each patient to determine the most suitable regimen for their patients.
Increased Risk of Stroke in Constipation Patients
Authors: Suenghataiphorn Thanathip , Yanpiset Panat , Xanthavanij Nutchapon , Srikulmontri Thitiphan , Thiravetyan Ben , Tribuddharat Narisara , Prasitsumrit Vitchapong , Danpanichkul Pojsakorn , Sodsri Tulaton , Kulthamrongsri Narathorn , Wattanachayaku Phuuwadith
Published: January 2025

Objective:

Constipation is commonly seen among patients with cardiovascular diseases and is linked to adverse outcomes. However, the association between constipation and the risk of stroke remains conflicting. Therefore, we aim to conduct a systematic review and meta-analysis to summarize the available data on this topic.

Methods:

We identified potentially eligible studies from the MEDLINE and EMBASE databases, searching from inception to May 2024, to investigate the association between constipation and stroke. To be included, studies needed to compare the incidence of stroke between groups with and without constipation. Effect size and 95% CIs were combined using the generic inverse variance method.

Results:

Our meta-analysis included 8 studies that met the eligibility criteria. There were 5,360,573 participants, with a mean age of 53.9 years and 69% are males. We found that patients with constipation have a 41% increased risk of stroke with a pooled risk ratio of 1.41 (95% CI: 1.13-1.75; P < 0.01, I
2 = 99%) compared with those without constipation. Subgroup analysis revealed that patients with constipation have a 50% increased risk of ischemic stroke with a pooled risk ratio of 1.50 (95% CI: 1.15-1.96; P < 0.01, I
2 = 99%), but no statistical significance was found for mixed-type stroke outcome.

Conclusions:

Our study revealed that constipation is associated with a higher risk of stroke. These findings could influence future strategies for cardiovascular disease prevention and management in patients with chronic constipation
Insights into proliferative glomerulonephritis with monoclonal immunoglobulin deposits – is it really monoclonal or not?
Authors: Nasr Samih H. , Javaugue Vincent
Published: January 2025

Purpose of review

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID), is a disease defined by the presence of glomerulonephritis with nonorganized mono-isotypic immunoglobulin (Ig) deposits. This review will discuss the pathogenesis of PGNMID and address novel techniques for detection of monoclonal Ig and pathologic B-cell clones and for distinguishing monoclonal from oligoclonal Ig deposits.

Recent findings

Because of low detection rate of circulating monoclonal Ig and nephritogenic B-cell clones and emerging reports of PGNMID-IgG in children, it has been recently argued that many PGNMID-IgG3 cases may not be monoclonal lesions. A mass spectrometry-based method, serum matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry, has been shown to have superior sensitivity than immunofixation for detection of monoclonal Ig in PGNMID and other monoclonal gammopathy of renal significance (MGRS) lesions. Two novel sequencing techniques, RNA-based immunoglobulin repertoire sequencing and single-molecule real-time sequencing of monoclonal immunoglobulin, enable identification of the full-length variable sequence of monoclonal Ig, even in MGRS patients with low tumor burden and undetectable monoclonal Ig by conventional methods. Finally, staining of kidney biopsy for Ig light chain variable domain subgroups may allow for separation of true monoclonal from oligoclonal PGNMID.

Novel sequencing, mass spectrometry, and immunofluorescence techniques have the potential to increase the detection rate of nephritogenic monoclonal Ig/B-cell clone and distinguish monoclonal from oligoclonal deposits in PGNMID.
Current status of neurotrauma management in resource-limited settings
Authors: Abdul-Rahman Toufik , Badar Sarah M. , Lee Sangeun , Wolfson Maximillian , Kundu Mrinmoy , Zivcevska Marija , Wireko Andrew Awuah , Atallah Oday , Roy Poulami , Davico Jazmin , Ogbuti Sharon , Ademeta Esther , Banimusa Sewar Basheer , Dmytruk Serhii , Teslyk Tetiana , Horbas Viktoriia
Published: January 2025

Over the last several decades neurotrauma has become recognized as a significant contributor to poor health outcomes, with growing physical, cognitive, social, and economic burdens. Although it serves as a significant contributor globally, it disproportionately affects low- and middle-income countries (LMIC). In this manuscript, we will be comparing how neurotrauma is managed across the globe with special consideration on how variations in environment, resources, infrastructure, and access can influence patient care and outcomes. Moreover, we will be examining the challenges faced by health care systems in LMIC and exploring strategies for quality improvement.
Assessing the influence of rapid diagnostic test (RDT) accuracy on malaria misdiagnosis and antimalarial resistance in Nigeria
Authors: Okereke Promise Udohchukwu , Ayodeji Bamimore Mubarak , Bolarinwa Roqeebat Titilope , Ayodeji Oluwatobi Deborah , Popoola Idris Olayemi , Okereke Wisdom Obumneme , Ogamba Nzubechukwu , Nworah Lilian Uzoma , Umeh Chukwuemeka Victor , Okpechukwu Chidubem Peter , Ibekwe Solomon Nnayelugo , Emeka Emmanuel , Tola Olalekan Simeon
Published: January 2025

Malaria remains a critical health challenge in tropical regions, demanding accurate and timely diagnosis to prevent severe negative outcomes. The disease’s misdiagnosis, driven by inadequate diagnostic tools, insufficient training, and systemic health care deficiencies, complicates effective management. Rapid diagnostic tests (RDTs), commonly used in Africa, often produce false-negative results due to various factors like parasite density and test conditions, which can lead to inappropriate treatment and potential drug resistance. Microscopy, while the gold standard, is often unavailable in resource-limited settings, pushing reliance on less accurate methods. Technological advances and improved education for health care workers are important for diagnostic accuracy. Innovations such as the Nanomal DNA analyzer, a point-of-care device, offer quick, reliable testing and the potential to identify drug resistance markers. The accuracy of malaria treatment can be significantly improved by integrating clinical assessments with refined diagnostic methods, reducing the disease burden in endemic areas. This comprehensive approach, combining technology, systemic health care improvements, and policy alignment, is important for effective malaria management and eventual eradication in affected regions.
Intraductal Polypoid Neoplasm in the Intrahepatic Large Bile Ducts of Small Duct-type Intrahepatic Cholangiocarcinoma May Result From Cancerization of Ducts
Authors: Nakanuma Yasuni , Kakuda Yuko , Matsubayashi Hiroyuki , Sugino Takashi
Published: January 2025

To survey and characterize intraductal polypoid neoplasms in the intrahepatic large bile ducts of small duct-type intrahepatic cholangiocarcinoma (small duct-iCCA), a total of 121 cases of small duct-iCCA presenting mass-forming growth were surveyed for intraductal polypoid neoplasms that were compared with mass-forming tumors in individual cases and with intraductal papillary neoplasm of bile duct (IPNB) (20 cases). Polypoid neoplasms were found in intrahepatic bile ducts in 8 (6.6%) of 121 cases of small duct-iCCA. They showed cast-like growth involving several adjoining bile ducts adjacent to or in the peripheries of mass-forming tumors as well as well-differentiated papillary or tubular/cribriform patterns and no stromal invasion. Intraductal polypoid neoplasms were histologically and immunohistochemically similar to mass-forming tumors in individual cases, and both components were of biliary subtype. There was an abrupt transition between these polypoid neoplasms and normal lining epithelia in the affected bile ducts, suggesting that intraductal polypoid neoplasms reflect the cancerization of ducts. IPNB presented with biliary (5 cases), intestinal (8 cases), gastric (5 cases), and oncocytic subtypes (2 cases), and about half of IPNBs were noninvasive, thus differing from intraductal polypoid neoplasms of small duct-iCCA. In conclusion, small duct-iCCA occasionally presents as intraductal polypoid neoplasms in adjoining bile ducts, reflecting the cancerization of ducts. These intraductal polypoid neoplasms should be considered in the differential diagnosis of heterogeneous intraductal tumors of bile ducts.
Expression and clinical significance of 25-hydroxyvitamin D, insulin-like growth factor 1, and beta-2 microglobulin in cognitive dysfunction after ischemic stroke in the elderly
Authors: Yang Huarong , Wu Qinhua , Zheng Jianghuan
Published: January 2025

We aimed to unveil the clinical significance of serum 25-hydroxyvitamin D (25-OH-VD), insulin-like growth factor 1 (IGF-1), and beta-2 microglobulin (β2-MG) levels in cognitive dysfunction after ischemic stroke (IS) in the elderly. A total of 160 geriatric IS patients admitted to our hospital were retrospectively collected. The patients’ serum 25-OH-VD, IGF-1, and β2-MG levels were detected, and the correlation between the three levels and the patients’ National Institutes of Health Stroke Scale (NIHSS) and Montreal Cognitive Assessment (MoCA) scores was tested by the Pearson test. The diagnostic values of 25-OH-VD, IGF-1, and β2-MG for cognitive dysfunction and risk factors inducing cognitive dysfunction in the elderly after IS were evaluated. NIHSS score was negatively correlated with serum 25-OH-VD and IGF-1 levels, and positively correlated with serum β2-MG levels; MoCA score exhibited an inverse correlation. Diabetes, years of education <12 years, age, and serum high-sensitive C-reactive protein, cystatin C, 25-OH-VD, IGF-1, and β2-MG levels were independent factors for the development of cognitive dysfunction after IS in the elderly. The detection of 25-OH-VD, IGF-1, and β2-MG may be important for assessing the occurrence of cognitive dysfunction and the severity of the disease in patients.
Identification of a distinctive gene signature in granulomatous myositis
Authors: Pinal-Fernandez Iago , Ruffer Nikolas , Casal-Dominguez Maria , Pak Katherine , Kleefeld Felix , Preusse Corinna , Kirou Raphael , Kinder Travis B. , Orso Stefania Del , Naz Faiza , Islam Shamima , Gutierrez-Cruz Gustavo , Milone Margherita , Selva-O’Callaghan Albert , Milisenda Jose C. , Schneider Udo , Liewluck Teerin , Stenzel Werner , Mammen Andrew L.
Published: January 2025

Objectives

Granulomatous myositis (GM) is defined by focal collections of activated macrophages that fuse to form multinucleated cells that aggregate into granulomas within skeletal muscle. This study aimed to elucidate the pathophysiology of GM by defining its specific transcriptomic profile.

Methods

Bulk RNA sequencing was performed on 722 muscle biopsies, including 38 from patients with GM, other myopathies, and healthy comparators. Spatial transcriptomics and immunohistochemistry assays were used to identify the location of specific transcripts and proteins within the tissue.

Results

The transcriptomic signature of GM muscle biopsies was characterized by high levels of IFNγ, IFNγ-inducible genes, and proinflammatory cytokine genes including IL1B, TNF, and TGFB1. The expression levels of 1293 specifically upregulated and 256 specifically downregulated genes were highly correlated with transcriptomic markers of disease activity. Support vector machine models using this gene set identified GM with an AUC of 99.6% (99.0%-99.9%) and an accuracy of 98.6% (98.2%-98.9%). Expression of CHIT1, the most significantly upregulated gene, strongly correlated with disease severity and was detected at the RNA and protein level in granulomas and giant cells.

Conclusions

GM is transcriptomically characterized by a strong IFNγ signature and overexpression of proinflammatory cytokines, including IL1B, TNF, and TGFB1. Additionally, it exhibits a unique transcriptomic profile, including CHIT1, which correlates with disease activity.
Theory of non-dilute binding and surface phase separation applied to membrane-binding proteins
Authors: Zhao Xueping , Sun Daxiao , Bartolucci Giacomo , Hyman Anthony A. , Honigmann Alf , Weber Christoph A.
Published: January 2025

Surface binding and surface phase separation of cytosolic scaffold proteins on lipid membranes are involved in many cellular processes, such as cell signaling, cell adhesion, and cortex regulation. However, the interplay between surface binding and surface phase separation is poorly understood. In this work, we study this interplay by deriving a general thermodynamic model and applying it to in vitro reconstitution experiments of membrane-binding proteins involved in tight junction initiation. Our theory extends the classical surface binding isotherm to account for non-dilute and heterogeneous conditions where components can phase separate. We use our theory to demonstrate how surface phase separation is governed by the interaction strength among membrane-bound scaffold proteins and their binding affinity to the membrane surface. Comparing the theory to reconstitution experiments, we show that tuning the oligomerization state of the adhesion receptors in the membrane controls surface phase transition and patterning of the scaffold protein ZO1. These findings suggest a fundamental role of the interplay between non-dilute surface binding and surface phase separation in forming the tight junction. More broadly, our work highlights non-dilute surface binding and surface phase separation as a common organizational principle for membrane-associated structures in living cells.
Optimal Inference of Asynchronous Boolean Network Models
Authors: Karlebach Guy
Published: January 2025

Associations between phenotype and genomic and epigenomic markers are often derived by correlation. Systems Biology aims to make more robust connections and uncover broader insights by modeling the cellular mechanisms that produce a phenotype. The question of choosing the modeling methodology is of central importance. A model that does not capture biological reality closely enough will not explain the system’s behavior. At the same time, highly detailed models suffer from computational limitations and are likely to overfit the data. Boolean networks strike a balance between complexity and descriptiveness and thus have received increasing interest. We previously described an algorithm for fitting Boolean networks to high-throughout experimental data that finds the optimal network with respect to the information in a given dataset. In this work, we describe a simple extension that enables the modeling of asynchronous dynamics, i.e. different reaction times for different network nodes. Our approach greatly simplifies the construction of Boolean network models for time-series datasets, where asynchronicty often occurs. We demonstrate our methodology by integrating real data from transcriptomics experiments, and provide an implementation that can be used by the community for network reconstruction using any high-throughout dataset. Our approach significantly expands the applicability of the Boolean network model to experimental data.
Cell Function Graphics: TOGGLE delineates fate and function within individual cell types via single-cell transcriptomics
Authors: Chen Junpeng , Chen Zhouweiyu , Sun Tianda , Jiang Eric , Liu Kaiqing , Nong Yibing , Yuan Tao , Daga Pawan , Dai Charles C. , Yan Yexing , Ge Jinwen , Wu Haihui , Yang Tong , Wang Shanshan , Su Zixiang , Song Tian , Abdelbsset-Ismail Ahmed , Li You , Li Changping , Singhal Richa A. , Yang Kailin , Carll Alex P.
Published: January 2025

Functional RNA plays a crucial role in regulating cellular processes throughout the life cycle of a cell. Identifying functional changes at each stage, from inception to development to maturation, functional execution, and eventual death or pathological transformation, often requires systematic comparisons of functional expression across cell populations. However, because cells of the same type often exhibit similar gene expression patterns regardless of function or fate, it is challenging to distinguish the stages of cellular fate or functional states within the same cell type, which also limits our understanding of cellular memory. Cells of the same type that share structural and gene expression similarities but originate from different regions and perform slightly distinct functions often retain unique epigenetic memory signatures. Although RNA serves as a key executor of fundamental cellular functions, its high expression similarity among cells of the same type limits its ability to distinguish functional heterogeneity. To overcome this challenge, we developed TOGGLE, utilizing higher-resolution analytical methods to uncover functional diversity at the cellular level. Then we based on TOGGLE developed an innovative Graph Diffusion Functional Map, which can significantly reduce noise, thereby more clearly displaying the functional grouping of RNA and enabling the capture of more subtle functional differences in high-dimensional data. Ultimately, this method effectively removes the influence of baseline functions from classification criteria and identifies key trajectories of cell fate determination.
Trust in physicians as a mediator of the relationship between person-centered care and medication adherence in patients undergoing hemodialysis: A cross-sectional study
Authors: Kanakubo Yusuke , Inanaga Ryohei , Toida Tatsunori , Aita Tetsuro , Ukai Mamiko , Kawaji Atsuro , Toishi Takumi , Matsunami Masatoshi , Munakata Yu , Suzuki Tomo , Okada Tadao , Kurita Noriaki
Published: January 2025

Rationale & Objective

Person-centered care (PCC) and trust in physicians influence medication adherence (MA) among patients undergoing dialysis. However, the mechanisms linking PCC to MA, particularly the mediating effect of trust in physicians, remain unclear. This study aimed to investigate the interrelationships between PCC, trust in physicians, and MA.

Study Design

Multicenter cross-sectional study.

Setting & Participants

Japanese adults receiving outpatient hemodialysis at six dialysis centers.

Exposures

PCC was assessed using the 13-item Japanese Primary Care Assessment Tool-Short Form, which included longitudinality and coordination of care. Trust in physicians was measured using the five-item Wake Forest Physician Trust Scale.

Outcome

MA was measured using the 12-item Adherence Starts Knowledge (ASK-12) scale.

Analytical Approach

General linear models were used to examine the relationships between PCC, trust in physicians, and MA. Mediation analysis determined the extent to which trust in physicians mediated the PCC-MA relationship.

Results

In total, 483 patients were analyzed. High-quality PCC was associated with lower barriers to MA in a dose-response manner across JPCAT-SF quartiles compared to no usual source of care (Q1: −3.90 (95% CI: −5.95 to −1.75); Q2: −4.78 (95% confidence interval [CI]: −7.02 to −2.69); Q3: −4.69 (95% CI: −6.96 to −2.58); Q4: −4.95 (95% CI: −7.21 to −2.62). Trust in physicians partially mediated this relationship in a dose-response pattern, with the proportion of the indirect effect increasing from 16.1% (95% CI: 4.5 to 33.8%) in Q2 to 33.3% (95% CI: 17.4 to 65.5%) in Q4. Similar findings were observed for PCC subdomains.

Limitation

Possible reverse causation.

Conclusions

High-quality PCC was associated with MA, with trust in physicians playing a key mediating role. Strategies to enhance MA in patients undergoing hemodialysis should incorporate multidimensional PCC approaches, focusing on building trust and strengthening continuity and coordination of care.
Transcriptomic analyses of human brains with Alzheimer’s disease identified dysregulated epilepsy-causing genes
Authors: Eteleeb Abdallah M. , Santos Alves Suélen , Buss Stephanie , Shafi Mouhsin , Press Daniel , Garcia-Cairasco Norberto , Benitez Bruno A.
Published: January 2025

Background & Objective

Alzheimer’s Disease (AD) patients at multiple stages of disease progression have a high prevalence of seizures. However, whether AD and epilepsy share pathophysiological changes remains poorly defined. In this study, we leveraged high-throughput transcriptomic data from sporadic AD cases at different stages of cognitive impairment across multiple independent cohorts and brain regions to examine the role of epilepsy-causing genes.

Methods

Epilepsy-causing genes were manually curated, and their expression levels were analyzed across bulk transcriptomic data from three AD cohorts and three brain regions. RNA-seq data from sporadic AD and control cases from the Knight ADRC, MSBB, and ROSMAP cohorts were processed and analyzed under the same analytical pipeline. An integrative clustering approach employing machine learning and multi-omics data was employed to identify molecularly defined profiles with different cognitive scores.

Results

We found several epilepsy-associated genes/pathways significantly dysregulated in a group of AD patients with more severe cognitive impairment. We observed 15 genes consistently downregulated across the three cohorts, including sodium and potassium channels, suggesting that these genes play fundamental roles in cognitive function or AD progression. Notably, we found 25 of these genes dysregulated in earlier stages of AD and become worse with AD progression.

Conclusion

Our findings showed that epilepsy-causing genes showed changes in the early and late stages of AD progression, suggesting that they might be playing a role in AD progression. We can not establish directionality or cause-effect with our findings. However, changes in the epilepsy-causing genes might underlie the presence of seizures in AD patients, which might be present before or concurrently with the initial stages of AD.
Looking for the optimal pathway to stimulate hippocampus in human participants using transcranial ultrasound stimulation (TUS): a simulation study
Authors: Lu Hanna , Li Zeyan , Ni Xi , Guo Liwei , Qiu Zhihai , Meng Lin , Yuan Yi
Published: January 2025

At present, very limited methods can directly modulate the neural activities in deep brain structures in human participants. Low-intensity transcranial ultrasound stimulation (TUS), as an emerging and advanced modality of non-invasive brain stimulation (NIBS), has great potential for focally stimulating the subcortical structures that are related to sleep, emotion and the functions of motor of cognition. Due to the focality, the integration of various methods, including magnetic resonance imaging and possible pathways, is important to perform TUS intervention for precise targeting and dosing. Based on structural MRI scans, we constructed a simulation model of low-intensity TUS, with a particular focus on the optimal pathways of targeting hippocampus in human participants. Finally, we outlooked the future perspectives of TUS in clinical applications in neurological and psychiatric fields.