bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of p16 in Hypertrophic Lichen Planus
Authors: Xu Katie R. , Honda Kord , Rohr Bethany R.
Published: February 2025

Background:

Although cutaneous squamous cell carcinoma (SCC) arising from lichen planus is rare, hypertrophic lichen planus (HLP) accounts for most of these malignant transformations. Although the mechanism of malignant pathogenesis remains unknown, reports of similar premalignant conditions suggest a potential role of tumor suppressor p16. This is the first study to our knowledge to examine p16 expression in HLP in comparison to cutaneous invasive SCC and normal skin and its implications for malignant transformation.

Methods:

p16 immunohistochemistry of HLP (n = 34) was performed alongside location-matched well-differentiated SCC (WDSCC) and normal skin. Percentage of positive cells, nuclear and cytoplasmic staining intensity, and staining distribution patterns were reviewed by 2 Board-certified dermatopathologists.

Results:

HLP and WDSCC both showed an increased percentage of positive cells compared with normal skin (P < 0.001). Cytoplasmic p16 was overexpressed in HLP compared with WDSCC (P < 0.05). Most cases of HLP and WDSCC demonstrated stronger basal and suprabasal keratinocyte staining with weaker superficial staining. In WDSCC, a predominant pattern of focal cytoplasmic margination of staining along the cellular periphery was observed.

Conclusions:

Our finding of cytoplasmic p16 overexpression in HLP suggests a potential mechanism of p16-mediated cell cycle dysregulation seen in other premalignant conditions. p16 overexpression seems to be a possible contributor in the malignant transformation of HLP to SCC.
Continuous ropivacaine wound infiltration versus epidural morphine after unplanned caesarean delivery
Authors: Bruillot Marine , Pieper Audrey , Sourd Dimitri , Roge Ana , Ramain Edith , Salah Samia , Bosson Jean-Luc , Payen Jean-Francois
Published: February 2025

BACKGROUND

Treatment programs designed to enhance recovery after caesarean delivery include multimodal analgesia to ensure optimal analgesia while reducing exposure to systemic opioids. Evidence for the effectiveness of continuous wound infiltration with local anaesthetic after unplanned caesarean delivery is needed.

OBJECTIVE

To determine whether continuous ropivacaine wound infiltration has noninferior analgesic properties compared to epidural morphine, while reducing side effects related to opioids.

DESIGN

Triple-blinded, noninferiority, randomised controlled trial.

SETTING

One university hospital, between February 2015 and August 2021.

PATIENTS

Eighty-one women undergoing unplanned lower segment caesarean section under epidural anaesthesia.

INTERVENTION

At the end of the procedure, randomly assigned patients received either an epidural bolus of 0.9% saline with 48 h continuous ropivacaine wound infusion (ropivacaine group) or an epidural bolus of morphine with 48 h 0.9% saline wound infusion (morphine group).

MAIN OUTCOME MEASURES

Pain during mobilisation at 24 h postsurgery was assessed using the visual analogue pain scale (VAS 0 to 10) with no indication of the allocated group.

RESULTS

Pain scores were 4.4 (95% CI, 3.6 to 5.1) in the ropivacaine group versus 3.1 (95% CI, 2.4 to 3.9) in the morphine group. The mean VAS pain difference between the two groups was 1.2 (95% CI, 0.2 to 2.3), which exceeded the prespecified noninferiority margin of 1. The differences between the two groups at rest and during mobilisation at 6 and 24 h were statistically significant. The ropivacaine group received rescue morphine more frequently, and were less satisfied despite fewer morphine-related side effects. Continuous wound infiltration was not technically feasible in 18% of the patients.

CONCLUSIONS

We failed to show that continuous ropivacaine wound infiltration was noninferior to epidural morphine in providing analgesia after unplanned caesarean delivery. Because of a significant rate of technical failures, continuous wound infiltration should only be considered when neuraxial morphine is contraindicated.
Current management of skin conditions in Kenya: exploring teledermatology preferences and perspectives among providers
Authors: Fernandez Jennifer M. , Kaderbhai Hashim , Adams Jennifer L. , Adam Mary B. , Adam Rodney D.
Published: February 2025

Background:

Teledermatology programs may help expand access to care for skin conditions in areas that are underserved by dermatologists such as sub-Saharan Africa, but their success requires input from participating providers.

Objective:

This study assesses teledermatology preferences among healthcare providers in Kenya.

Methods:

An anonymous cross-sectional survey of nondermatology providers was conducted in Kenya from January to March 2024 at Aga Khan University Hospital-Nairobi and Kijabe Hospital.

Results:

Among the 38 providers, 81.6% were physicians. Patient population was primarily Fitzpatrick skin types V and VI. Almost all (97.4%) regularly encountered patients with skin disorders, yet only 5.3% felt comfortable diagnosing and treating 80 to 100% of these disorders independently. Providers anticipated referring cases of rashes (76.3%), unclear diagnoses (63.2%), and infectious diseases (50%), among others, for teledermatology consultation. Only 10.5% reported utilizing teledermatology, although the majority believed it would be useful (91.9%) and improve patient care (89.5%). Preferred response time was <24 hours (81.6%). Most favored submitting cases via personal cell phones (86.8%), with 87.9% preferring submission through WhatsApp.

Limitations:

Participants owned smartphones. The survey was distributed via WhatsApp.

Conclusion:

Nearly all providers in Kenya see patients with skin conditions, but few utilize teledermatology services. Teledermatology could be extremely beneficial for patients and providers seeking dermatologic expertise.
Effectiveness of intravenous lidocaine in treatment of burn pain: a systematic review and meta-analysis of randomised controlled trials
Authors: Elgadi Ammar , Mohmed Ahd , Elbadawi Mohamed H , Elawad Shaima O , Elamin Mohamed Yousif , Elhaj Nida Bakri , Elsadig Ahmed , Abdallah Hayat
Published: February 2025

Background:

Burns are among the most agonizing injuries encountered in the clinical setting. Protocols for effective management of burn pain vary and mostly rely on opioids, a drug class well-known for dependence and adverse effects from misuse. Lidocaine, the most commonly used local anesthetic has shown potential to reduce the amount of opioids required. This study aims to assess the effectiveness of lidocaine infusion in reducing opioid use in patients with burn injuries.

Materials and methods:

This systematic review was conducted according to PRISMA guidelines. A comprehensive search of the electronic databases was carried out using the keywords “lidocaine,” “lignocaine,” “xylocaine,” “burn,” and “analgesia.” Eligible studies were randomised control trials (RCTs) from peer-reviewed journals or registries. Two independent reviewers conducted the screening. The Cochrane ROB-2 Tool was used to assess the quality of the included studies. Meta-analysis was conducted using Revman software.

Results:

We included four RCTs with 152 burn patients with total body surface area (TBSA) burned ranged from 3% to 68%. Morphine use had a standardized mean difference (SMD) of −0.47 [−1.18 to 0.24], which was not significant (p = 0.19). The changes in pain score weren’t significant (SMD = − 0.01, CI = [−0.37; 0.34], p = 0.94). Nausea had RR of 1.06 (CI = [0.80; 1.40], p = 0.700). No serious adverse event was reported.

Conclusion:

Our findings were inconclusive about the safety and effectiveness of lidocaine as an adjunct in the analgesia of burns and reducing the required opioid dosage. Large-scale clinical trials are needed.
Rivaroxaban versus dalteparin for the treatment of cancer-associated venous thromboembolism: a systematic review and meta-analysis
Authors: Shrestha Bibek , Bhusal Suzit , Kandel Grishma , Bastakoti Sudip , Yadav Krishna Kumar
Published: February 2025

Background and Aims:

Traditionally, low molecular weight heparin (LMWH), such as dalteparin, has been the first-line treatment for cancer-associated VTE. However, recent studies suggest that rivaroxaban, a direct oral anticoagulant, may offer comparable efficacy with the convenience of oral administration. This systematic review and meta-analysis aim to evaluate and compare the efficacy and safety of rivaroxaban versus dalteparin in managing cancer-associated VTE, focusing on recurrence rates, bleeding events, and patient adherence.

Methods:

This review follows the PRISMA guidelines, systematically retrieving data from PubMed and Cochrane databases using structured search terms related to cancer, VTE, and anticoagulation. Data on recurrent VTE, major bleeding, and patient outcomes were extracted, Statistical analyses were performed using a random-effects model to account for heterogeneity.

Results:

Nine studies were analysed, encompassing a range of study designs across multiple countries. The findings show no significant difference in major bleeding risk between rivaroxaban and dalteparin (RR 0.91, p = 0.69), nor in bleeding-related mortality (OR 4.00, p = 0.36). Rivaroxaban was associated with a significant reduction in DVT recurrence (OR 0.75, p = 0.04) and a marginally non-significant reduction in PE recurrence (OR 0.73, p = 0.05). Non-significant bleeding events were slightly higher with rivaroxaban but did not reach statistical significance.

Conclusion:

Rivaroxaban presents a viable alternative to dalteparin for treating cancer-associated VTE, showing comparable safety regarding major bleeding and potential efficacy in reducing DVT recurrence. This study supports the potential for more standardized guidelines that include rivaroxaban as a feasible option in cancer-associated VTE management.
Revolutionizing breast cancer monitoring: emerging hematocrit-based metrics- a narrative review
Authors: Obeagu Emmanuel Ifeanyi , Obeagu Getrude Uzoma
Published: February 2025

Breast cancer remains a leading global health concern, with significant strides made in early detection and treatment. However, effective long-term surveillance, particularly for recurrence and metastasis, remains a clinical challenge. Traditional methods like imaging and biopsy are often invasive, costly, and have limited sensitivity in detecting subtle changes during disease progression. Emerging evidence suggests that hematocrit-based metrics—measurements of the proportion of red blood cells (RBCs) in blood—could serve as valuable, minimally invasive biomarkers for monitoring breast cancer. This review highlights recent advancements in hematocrit-focused research and its potential role in revolutionizing breast cancer surveillance. Hematocrit dynamics reflect complex physiological processes influenced by cancer biology, including inflammation, angiogenesis, and treatment-induced bone marrow suppression. Alterations in hematocrit levels have been associated with prognostic outcomes, treatment responses, and early indications of recurrence in breast cancer patients. Coupled with other hematological and molecular markers, hematocrit offers a cost-effective and readily accessible tool to track disease status in real time. Recent technological innovations, such as point-of-care testing, artificial intelligence-driven data analysis, and microfluidic devices, are further advancing the applicability of hematocrit-based metrics in both clinical and remote monitoring settings.
“Aprocitentan in hypertension management: clinical efficacy, safety, and future prospects”
Authors: Riaz Rumaisa , Ahmed Usaid , Naqi Unaiza , Afaq Laiba , Shaukat Ayesha , Khan Yalnaz , Akilimali Aymar
Published: February 2025

Hypertension (HTN) is a prevalent medical condition characterized by systolic blood pressure (SBP) ≥ 130 mm Hg and diastolic blood pressure (DBP) ≥ 80 mm Hg. In 2010, the global prevalence of hypertension was 31.1%, with higher rates in men and low- and middle-income countries (LMICs). The etiology of primary hypertension involves neurohumoral, renal, metabolic, genetic, and environmental factors, with the kidneys playing a significant role in long-term blood pressure regulation. Endothelin-1 (ET-1), a potent vasoconstrictor, contributes to hypertension by affecting salt-water balance and promoting vascular remodeling. Hypertension often presents without symptoms, leading to complications such as heart failure, stroke, and renal failure if untreated. Common treatment options include angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), and diuretics. Aprocitentan, a novel dual endothelin receptor antagonist, has shown promise in reducing blood pressure in patients with resistant hypertension. Clinical trials, including the Phase 3 PRECISION study, demonstrated its efficacy and long-term control. However, Aprocitentan’s use is associated with safety concerns, such as hepatotoxicity, fluid retention, and embryo-fetal toxicity, necessitating careful monitoring. Aprocitentan represents a significant advancement in hypertension management, offering a new therapeutic option for patients with uncontrolled hypertension, although vigilant monitoring and informed decision-making are essential to mitigate potential risks and ensure optimal outcomes.
MRSA-positive sternoclavicular septic arthritis mimicking mediastinal malignancy in a patient with multiple injection history: a rare case report
Authors: Shakeel Muzammil , Saleem Saad , Ali Huzafa , Saqib Huzaifa , Adhikari Dipendra , Nazeef Ayesha , Tariq Aisha , Ud–Din Zeeshan , Kamran Maheen
Published: February 2025

Introduction and importance:

Infection of the sternoclavicular joint is exceptionally rare, accounting for less than 1% of bone infections. The presence of MRSA-positive septic arthritis in the sternoclavicular joint, coupled with its resemblance to mediastinal conditions and a history of multiple injections, presents a rare and complex clinical case that demands thorough evaluation and management.

Case presentation:

A 60-year-old male with a complex medical history, including hypertension, diabetes mellitus, hepatitis C, and recurrent cellulitis due to multiple IV and IM injections, presented with drowsiness and a painful, erythematous swelling of the left anterior chest wall. Clinical examination revealed pallor, distended abdomen, and decreased left-sided airway entry. Diagnostic workup showed elevated creatinine, metabolic acidosis, and inflammatory markers. Imaging revealed extensive soft tissue swelling and a mediastinal mass. A core biopsy confirmed severe acute and chronic inflammation, abscess formation, and granulation tissue suggestive of an infectious etiology. CT scans further identified sternoclavicular septic arthritis, a rare diagnosis.

Clinical discussion:

This case report describes MRSA-positive sternoclavicular septic arthritis in a patient with a history of tramadol and multivitamin injections. Sternoclavicular joint (SCJ) infection is rare, complicating differentiation from mediastinal malignancies. Successful management required embolization, IV antibiotics, and physiotherapy.

Conclusion:

MRSA-positive sternoclavicular septic arthritis, mimicking mediastinal malignancy, presents diagnostic challenges. Successful management involves tailored strategies, interdisciplinary collaboration, and consideration of IV drug injections.
Effect of osteopathic manipulative treatment on pain in palliative care patients: a randomized placebo-controlled clinical trial
Authors: Galeazzi Yann , Houel Nicolas , Gouaux Léa , Rohan Anne , Le Heiget Hélène , Jung Camille , Housset Bruno , Stubbe Laurent
Published: February 2025

Introduction:

Standard osteopathic manipulative therapy (OMT) is used as a supportive care for pain management in cancer patients.

Objectives:

The present study aimed to compare the efficacy of OMT with that of a sham treatment to attenuate pain in cancer patients in a palliative care unit.

Methods:

This randomized clinical trial was a simple blind, monocentric, placebo-controlled study. Seventy-five patients were randomly distributed between standard and sham OMT sessions at a 1:1 ratio, receiving standard or sham treatment every 2 days for the 7 days of the study. Patients were assessed using a self-administered visual analog scale (VAS)—ranging from 0 to 100, recorded in the morning and evening. They also completed the QLQ-C15-PAL quality-of-life questionnaire on the first and last day of the study. For participants with controlled analgesia pumps, the number of analgesic doses was recorded.

Results:

The OMT group demonstrated a significant effect of days, circadian period, and group on VAS pain decrease (P < 0.05). The VAS pain score for the OMT group exhibited a notable decline from the third day (D3 pm) (P = 0.03) to D6 pm (P = 1.28 × 10−05) with 43.2% improvement by the conclusion of the study. On D6, the quality-of-life score exhibited a tendency towards improvement. Patients with analgesia pumps showed a 31.58% reduction in their demand for analgesics (P = 0.016). No significant results were observed between D0 and D3.

Conclusion:

It is hypothesized that OMT could prove an efficacious method of pain management in cancer patients receiving palliative care, in addition to conventional cancer treatment.
Forecasting migraine attacks by managing daily lifestyle: a systematic review as a basis to develop predictive algorithms
Authors: Quartetti Umberto , Brighina Filippo , Gambino Giuditta , Frinchi Monica , Bellafiore Marianna , Tabacchi Garden , Vasto Sonya , Accardi Giulia , Amato Antonella , Giardina Marta , Mazzucco Walter , Boffetta Paolo , Giglia Giuseppe , Di Liberto Valentina
Published: February 2025

Recent studies attempting to develop forecasting models for new migraine attack onsets, overviewing triggers and protectors, are encouraging but necessitate further improvements to produce forecasting models with high predictive accuracy. This updated review of available data holds the potential to enhance the precision of predicting a migraine attack. This study aims to evaluate how lifestyle factors affect migraine frequency in adults with episodic migraine, to contribute to the development of an effective migraine forecasting model. A comprehensive search of databases, including PubMed, ScienceDirect, Google Scholar, and Scopus, was conducted considering studies published from 2018 to December 2023, following the PRISMA guidelines. Critical evaluation was conducted using the Joanna Briggs Institute's appraisal tools. The lifestyle modifications examined in this review included dietary habits, physical activity, sleep, and stress management. Of the 36 studies analysed, which predominantly exhibited low to moderate bias, 18 investigated dietary habits, 7 explored physical activity, 11 assessed stress management, and 5 investigated sleep patterns. The evidence from these 36 studies advocates for the implementation of lifestyle modifications in migraine management. Furthermore, these outcomes carry valuable implications from the standpoint of migraine forecasting models. The most consistent results were observed in relation to specific diets, dietary supplements, and physical activity. Although trends were noted in stress management and sleep, further research is required to elucidate their influence on migraine frequency and their integration into a migraine forecasting model. This study is registered on PROSPERO (ID CRD42024511300).
Reduced peri-pubertal bone density accrual among Zimbabwean males living with HIV: a longitudinal study
Authors: Jeena Lisha , Ferrand Rashida A. , Simms Victoria , Kahari Cynthia , Bandason Tsitsi , Rukuni Ruramayi , Rehman Andrea M. , Rowland-Jones Sarah , Hsieh Anthony Y.Y. , Gregson Celia L.
Published: February 2025

Objective:

To investigate bone density accrual over 1 year among peripubertal children living with HIV (CWH) compared to children without infection (CWOH); and risk factors associated with bone density accrual among CWH.

Design:

A prospective cohort study in urban Zimbabwe.

Methods:

CWH on antiretroviral therapy aged 8–16 years, and CWOH, frequency-matched by age were recruited in Zimbabwe. Z-scores for height-adjusted total-body less-head bone mineral content for lean mass (TBLH-BMCLBM) and size-adjusted lumbar spine bone mineral apparent density (LS-BMAD) were calculated from dual X-ray absorptiometry (DXA) scan measurements. Linear regression compared bone density accrual by HIV status.

Results:

Of 609 participants, 492 (80.7%) completed a follow-up visit (50.2% male, 49.6% CWH). Mean baseline age was 12.5 years. More female CWH than CWOH were in Tanner stages I/II at baseline. Bone density accrual (Δ) adjusted for age, Tanner stage and baseline DXA Z-score was less in male CWH than male CWOH {adjusted mean (95% confidence interval (CI)] ΔLS-BMAD Z-score −0.14 (−0.25 to −0.02) vs. 0.01 (−0.09 to 0.12), P = 0.020, and ΔTBLH-BMCLBM
Z-score −0.19 (−0.33 to −0.04) vs. 0.07 (−0.07 to 0.20), P = 0.015}, but similar in females with and without HIV [ΔLS-BMAD Z-score 0.05 (−0.07 to 0.17) vs. −0.01 (−0.09 to 0.07), P = 0.416, and ΔTBLH-BMCLBM
Z-score 0.08 (−0.07 to 0.22) vs. −0.03 (−0.12 to 0.07), P = 0.295]. Viral load greater than 1000 copies/ml and tenofovir disoproxil fumarate use were associated with less gain in LS-BMAD Z-score among males, whereas Tanner stage IV and V were associated with greater gains in LS-BMAD and TBLH-BMCLBM
Z-scores among CWH.

Conclusion:

Among males only, CWH had impaired bone accrual, associated with high viral load and tenofovir use. Bone density gains were greater in later puberty among CWH suggesting potential to correct deficits.
Physical, psychosocial and sexual health among people aged 50 years and above with and without HIV: a nationwide study
Authors: Scofield Ditte , Frisch Morten , Andersson Mikael , Storgaard Merete , Pedersen Gitte , Johansen Isik S. , Katzenstein Terese L. , Graugaard Christian , Omland Lars H. , Weis Nina , Moseholm Ellen
Published: February 2025

Objective:

To investigate physical, psychosocial and sexual health outcomes in ≥50 years-old people with and without HIV.

Design:

Cross-sectional study in Denmark comparing health outcomes by HIV status.

Methods:

Data were drawn from the SHARE study, a nationwide survey conducted between 2021 and 2022, examining psychosocial, sexual and reproductive health in people with HIV (PWH), and compared to data from people without HIV (PWOH) in the nationally representative Project SEXUS cohort study. Health outcomes were assessed using validated patient-reported outcome measures, with sex-stratified logistic regression models adjusting for sociodemographic and other confounding factors.

Results:

The study included 322 men and 67 women with HIV and 15 548 men and 13 926 women without HIV. PWH were more likely to report being single and having non-Danish parentage. HIV was associated with higher odds of liver disease in both men and women, cardiovascular and lung diseases in men, and osteoporosis and hypertension in women. Compared with PWOH, men with HIV more often reported depressive symptoms or a history of treatment for anxiety, while women with HIV more often reported loneliness, suicidal thoughts and domestic abuse. Sexually, PWH more often reported reduced sexual desire and activity, men with HIV more often reported erectile dysfunction or orgasmic dysfunction and women with HIV more often reported lubrication dysfunction or genital pain dysfunction.

Conclusions:

PWH aged ≥50 years in Denmark face significantly more physical, psychosocial and sexual health challenges than PWOH. Clinical attention to these disparities is crucial for improving the overall health of ageing PWH.
Cerebrospinal fluid biomarkers of inflammation and immune activation associated with neurocognitive impairment among U.S. Latinos living with HIV
Authors: Diaz Monica M. , Kamalyan Lily , Al-rousan Tala , Breton Jordana , Franklin Donald R. , Umlauf Anya , Ellis Ronald J. , Cherner Mariana , Iudicello Jennifer , Heaton Robert K. , Letendre Scott L. , Marquine María J.
Published: February 2025

Objective:

Examine the association between markers of inflammation in the cerebrospinal fluid (CSF) and neurocognitive impairment (NCI) among diverse persons with HIV (PWH).

Background:

Latino PWH are at higher risk for NCI than non-Latino White PWH (NLW). Evidence of inflammation in cerebrospinal fluid (CSF) can be higher among racial and ethnic minority PWH and has been linked to NCI.

Methods:

We performed a retrospective cross-sectional analysis of 363 PWH who identified as Latinos or NLW. Neurocognitive performance was measured by a comprehensive battery. A focused panel of biomarkers [interleukin-6 (IL-6), soluble CD14 (sCD14), interferon-γ-inducible protein-10 (IP-10), neurofilament light chain (NFL)] was measured in CSF by immunoassay. Covariates included demographic, HIV disease, medical, psychiatric, and substance use characteristics.

Results:

The cohort consisted of 126 Latinos and 237 NLW (age: M = 42.5, SD = 11.0, 88% male, 51.5% AIDS history; 64% on antiretroviral therapy). Latinos had significantly higher NFL levels than NLW (P < 0.0001, adjusted Cohen's d 1.15), but not among virally-suppressed PWH. In the entire cohort, higher sCD14 was associated with NCI (adjusted odds ratio (aOR) = 2.6, confidence interval (CI) = 1.1–6.5] after adjusting for statistically significant covariates.

Conclusions:

We did not identify a relationship between ethnicity, inflammation and NCI in this cohort. Future studies might examine sociocultural factors leading to increased inflammation in the CSF in diverse PWH.
Early Autologous Fat Grafting for Facial Lipoatrophy Caused by Undifferentiated Connective Tissue Disease
Authors: Xiao Yiding , Zhou Jingyang , Zhu Xingyu , Wang Yang
Published: February 2025

A variety of autoimmune disorders that do not fit the criteria for specific connective tissue diseases are included in the category of undifferentiated connective tissue disease (UCTD). Facial lipoatrophy is an underreported presenting characteristic, despite the prevalence of cutaneous symptoms. The aim of this article is to demistrate the potential of early autologous fat grafting (AFG) in treating facial depressions caused by UCTD. A 29-year-old woman with UCTD presented with progressive bilateral cheek depressions and was managed with tacrolimus lately. Sheet-like depressions can be found during physical examination, which are more pronounced on the left cheek. The patient underwent AFG surgery to the affected areas. During the surgery, a total of 30 mL of fat was harvested from the lower abdomen, and 5.0 mL of pure fat was eventually gained and grafted to the bilateral cheek depressions. Satisfying aesthetic outcomes were achieved with smooth facial contours. Through the use of adipose-derived stem cells, early AFG in the active stage of UCTD can enhance face appearance while also possibly having local anti-inflammatory and antifibrotic benefits. It also has important implications for improving the look and slowing the progression of other autoimmune diseases that affect the face.
Remote Site Delayed Extradural Hematoma Secondary to Decompressive Craniectomy for Traumatic Brain Injury: Incidence, Predictors, Characteristics, and Outcomes
Authors: Shen Jun , An Qian , Cao Jun , Fang Jingcheng , Xia Dayong , Jiang Xiaochun , Zhang Shaolin
Published: February 2025

Objective:

Remote site delayed extradural hematoma (RDEDH) is an uncommon but serious complication that can occur after decompressive craniectomy (DC) in patients with traumatic brain injury (TBI). This study aims to clarify the incidence, predictors, clinical and radiological characteristics, and outcomes of RDEDH to improve the authors' understanding and management of this complication.

Methods:

This study identified 36 patients with TBI who developed RDEDH after DC. The incidence, predictors, clinical and radiological characteristics, and outcomes were analyzed retrospectively. Continuous variables were compared using the student t test, whereas categorical variables were assessed using the χ2 test. Variables with a P value of <0.05 in univariable analysis were included in the multivariable logistic regression analysis.

Results:

The incidence of RDEDH after DC was 14.6%. Preoperative pupillary dilation [bilaterally; odds ratio (OR): 8.797; 95% CI: 1.969–39.297; P = 0.004], intraoperative acute brain swelling (OR: 33.696; 95% CI: 5.073–227.005; P < 0.001), and pupillary abnormalities after DC (OR: 8.141; 95% CI: 2.117–31.307; P = 0.002) were identified as independent risk factors for the development of RDEDH after DC. The average length of hospitalization in the RDEDH group was significantly longer than that in the non-RDEDH group (P = 0.018). The Glasgow Outcome Scale score at 6 months in the RDEDH group was significantly lower than that in the non-RDEDH group (P = 0.01). The incidence of poor prognosis in the RDEDH group (80.6%) was significantly higher than that in the non-RDEDH group (59.8%; P = 0.017).

Conclusion:

Preoperative bilateral pupillary dilation, intraoperative brain swelling, and pupillary abnormalities after surgery were independent risk factors for the development of RDEDH after DC in patients with TBI. The occurrence of RDEDH in patients with TBI after DC did not significantly increase mortality, it was associated with a prolonged length of stay and an increased incidence of poor prognosis.
Open Globe Injury After Penetrating Keratoplasty: Etiology and Prognostic Factors
Authors: Özer Ömer , Dursun Özer
Published: February 2025

Background:

This study aimed to evaluate the etiologic causes and prognostic factors affecting the final outcome of patients with open globe injury after penetrating keratoplasty.

Methods:

This study included patients between November 2018 and June 2024. Age, sex, intraocular pressure (mm Hg), visual acuity (logMAR), indication for keratoplasty, time since keratoplasty, cause, location, and length of injury were noted. All patients were followed up for at least 3 months after surgery.

Results:

There was a moderate positive correlation between visual acuity in the first month and the third month after trauma repair (r=0.562, P=0.036). Final visual acuity was 1.0 logMAR or worse in high injury length patients (6 clocks or more). Patients with vitreous loss had a final visual acuity of 0.9 logMAR or worse. Of the 5 patients who underwent PK for keratoconus, 4 (80%) had visual acuity of 1.2 logMAR or worse at the third month after trauma.

Conclusion:

In conclusion, final visual acuity is poor in patients who underwent PK due to high injury length, vitreous loss, and keratoconus. In addition, final visual acuity is associated with visual acuity in the early postoperative period. Patients undergoing PK should be informed about globe injuries, risks of visual loss, and protective precautions. Patients should also be enlightened about wound healing and encouraged to prevent trauma.
Mitochondrial Transplantation
Authors: Mukkala Avinash Naraiah , David Bruna Araujo , Ailenberg Menachem , Liang Jady , Vaswani Chirag Manoj , Karakas Danielle , Goldfarb Rachel , Barbour William , Gasner Avishai , Wu Ruoxian Scarlet , Petrut Raluca , Jerkic Mirjana , Andreazza Ana C. , dos Santos Claudia , Ni Heyu , Zhang Haibo , Kapus Andras , Kubes Paul , Rotstein Ori David
Published: February 2025

Objective:

To investigate the hepatoprotective effects of mitochondrial transplantation in a murine liver ischemia/reperfusion (I/R) model.

Summary Background Data:

Sequential liver ischemia followed by reperfusion (I/R) is a pathophysiological process underlying hepatocellular injury in a number of clinical contexts, such as hemorrhagic shock/resuscitation, major elective liver surgery and organ transplantation. A unifying pathogenic consequence of I/R is mitochondrial dysfunction. Restoration of mitochondria via transplantation (MTx) has emerged as potential therapeutic in I/R. However, its role in liver I/R and its mechanisms of action remain poorly defined.

Methods:

We investigated the hepatoprotective effects of MTx in an in vivo mouse model of liver I/R and used in vivo imaging and various knockout and transgenic mouse models to determine the mechanism of protection.

Results:

We found that I/R-induced hepatocellular injury was prevented by MTx, as measured by plasma ALT, AST and liver histology. Additionally, I/R-induced pro-inflammatory cytokine release (IL-6, TNFα) was dampened by MTx, and anti-inflammatory IL-10 was enhanced. Moreover, MTx lowered neutrophil infiltration into both the liver sinusoids and lung BALF, suggesting a local and distant reduction in inflammation. Using in vivo intravital imaging, we found that I/R-subjected Kupffer cells (KCs), rapidly sequestered transplanted mitochondria, and acidified mitochondria within lysosomal compartments. To specifically interrogate the role of KCs, we depleted KCs using the diphtheria toxin-inducible Clec4f/iDTR transgenic mouse, then induced I/R, and discovered that KCs are necessary for the beneficial effects of MTx. Finally, we induced I/R in complement receptor of the immunoglobulin superfamily (CRIg) knockout mice and found that CRIg was required for mitochondria capture by KCs and mitochondrial-mediated hepatoprotection.

Conclusions:

In this study, we demonstrated that CRIg-dependent capture of mitochondria by I/R-subjected Kupffer cells is a hepatoprotective mechanism in vivo. These data progress knowledge on the mechanisms of MTx and opens new avenues for clinical translation.
Selection and maintenance of mobile linezolid-resistance genes and plasmids carrying them in the presence of florfenicol, an animal-specific antimicrobial
Authors: Fukuda Akira , Usui Masaru
Published: February 2025

Mobile linezolid-resistance genes (optrA, poxtA, and cfr) that confere resistance to linezolid and florfenicol have been detected globally in various sources. Linezolid is a last-resort antimicrobial used in human clinical settings, and florfenicol is commonly used in veterinary clinical settings. The present study sought to evaluate the potential of florfenicol in veterinary use to select for linezolid-resistant bacteria. The growth and fitness of linezolid-resistant bacteria harboring mobile linezolid-resistance genes were assessed in the presence and absence of florfenicol using Enterococcus faecalis and E. faecium, respectively. The bacterial strains harbored wild and cloning plasmids carrying mobile linezolid-resistance genes, which reduced their susceptibility to linezolid and florfenicol. The acquisition of plasmids carrying mobile linezolid-resistance genes improved bacterial growth in the presence of florfenicol, and conferred fitness costs in its absence. Florfenicol imposes a selection pressure on bacteria harboring plasmids carrying mobile linezolid-resistance genes. Hence, the appropriate use of florfenicol in veterinary clinical settings is important to control the dissemination of mobile linezolid-resistance genes and to ensure the sustained effectiveness of linezolid against multidrug-resistant bacteria, including vancomycin-resistant enterococci in human clinical settings.
Campylobacter molothri sp. nov. isolated from wild birds
Authors: Miller William G. , Lopes Bruno S. , Chapman Mary H. , Williams Tina G. , Ramjee Meenakshi , Wood Delilah F. , Bono James L. , Forbes Ken J.
Published: February 2025

Twenty-nine hippuricase-positive Campylobacter strains were isolated from wild birds and river water. Previous characterization using atpA typing indicated that these strains were related to Campylobacter jejuni and Campylobacter coli but were most similar to three recently described hippuricase-positive Campylobacter species recovered from zebra finches, i.e. C. aviculae, C. estrildidarum and C. taeniopygiae. Phylogenetic analyses using 330 core genes placed the 29 strains into a clade well separated from the other Campylobacter taxa, indicating that these strains represent a novel Campylobacter species. Pairwise digital DNA–DNA hybridization and average nucleotide identity values were below 70 and 95 %, respectively, thus providing further supporting evidence of a novel taxon. Standard phenotypic testing was performed. All strains are microaerobic or anaerobic, motile, Gram-negative, spiral cells that are oxidase, catalase and nitrate reductase positive, but urease negative. Genomic analyses indicate that the 29 strains can potentially synthesize very few amino acids de novo and are auxotrophic for many amino acids and cofactors, similar to the species composing the Campylobacter lari group. In addition, these strains encode complete Entner–Doudoroff and Leloir pathways, suggesting that they may possess the ability to utilize both glucose and galactose; these pathways were also identified in the genomes of the zebra finch-associated taxa. The data presented here show that these strains represent a novel species within Campylobacter, for which the name Campylobacter molothri sp. nov. (type strain RM10537T=LMG 32306T=CCUG 75331T) is proposed.
Phylogeography and diversification of thePieris napispecies group in the Western Palaearctic
Authors: Sala-Garcia Javier , Vives-Ingla Maria , Tonzo Vanina , Dincă Vlad , Vila Roger , Carnicer Jofre
Published: February 2025

The butterflies of thePieris napicomplex, encompassing diverse taxa across Europe, Asia and North Africa, represent an emergent model system for studying climatic adaptation. In this study, we use genomic data for this group to address phylogenetic relationships, population structure and ecological differentiation in the Western Palearctic. Our results reveal two main groups: thenapiclade and thebryoniae-balcanaclade. We clarify the status and show that the distribution of the debated speciesP. balcanaextends to south Romania and the Peloponnese. This species is shown to be sister toP. bryoniae, which indicates that melanism is an evolutionarily labile trait linked to climatic adaptation. TheP. napiclade is divided into three components, each predominating in a different south European peninsula, and the borealP. n. adalwinda, which is notably differentiated. The endangered Moroccan taxonsegonzaciproduced conflicting results, probably due to low-quality DNA. Admixture analyses suggest substantial gene flow between taxa in contact areas. Redundancy analyses identify summer temperature and precipitation as key drivers of adaptive genetic variation within the group. This work provides a robust evolutionary framework for future ecological studies of thePieris napicomplex, to forecast eco-evolutionary responses and to address conservation priorities in a rapidly changing climate.
Hepatic Arterial Flow-Induced Portal Tract Fibrosis in Portal Hypertension: The Role of VCAM-1 and Osteopontin-Expressing Macrophages
Authors: Ma Ruixue , Gong Li , Dong Chao , Utsumi Teruo , Qi Jiewen , Zhuang Zhen W. , Zhang Xuchen , Yang Yilin , McConnell Matthew J. , Huang Hui-Chun , Iwakiri Yasuko
Published: February 2025

Background

The liver undergoes significant hemodynamic changes during surgery, transplantation, or cirrhosis with portal hypertension(PH). The hepatic artery buffer response(HABR), which compensates for reduced portal venous flow by increasing hepatic artery(HA) flow, is hypothesized to induce pathological portal tract remodeling. This study investigates the molecular mechanisms underlying this process.

Methods

PH was induced in Sprague-Dawley rats via partial portal vein ligation(PPVL). Structural evaluation(microCT), immune cell profiling, hemodynamic measurements, and transcriptomic analysis in macrophages(Mϕ) from sham or PPVL rats were conducted.

Results

MicroCT revealed decreased portal vein flow and increased HA flow correlated with portal pressure(r=0.799, p<0.01). A 2-fold increase in portal tract fibrosis(p<0.001) was observed with increased α-SMA+ myofibroblasts in PPVL rats. CD68+ Mϕ peaked at 10 days post-PPVL, and their depletion significantly reduced fibrosis(p<0.001), indicating critical roles of Mϕ in portal tract remodeling. VCAM-1 was elevated in HA endothelium and portal fibroblasts (PFs); VCAM-1 neutralization reduced collagen accumulation(p<0.05), CD68+ Mϕ(46.3%, p<0.01), and CD3+ T cells(18%, p<0.05). Mϕ-conditioned medium increased VCAM-1 in PFs(8-fold, p<0.001) and enhanced PF migration, while VCAM-1 knockdown reduced this effect (p<0.01). Single-cell RNA sequencing data(GSE171904) and RNA-FISH revealed increased interactions between osteopontin (Spp1)+ Mϕ and PFs, with Spp1+ Mϕ driving fibrosis. Spp1 knockdown in Mϕ co-culture reduced PF fibrogenic markers, while recombinant Spp1 upregulated Col1a1, Fn1, and Acta2 expression in PFs.

Conclusion

Increased VCAM-1 in arterial endothelial cells and PFs facilitates the recruitment of Spp1+ Mϕ, which drive HA flow-mediated vascular remodeling and portal tract fibrosis. These findings highlight arterial flow-induced fibrosis as a key mechanism in PH, potentially contributing to disease progression and decompensation.

Synopsis

Liver hemodynamic changes in portal hypertension drive extracellular matrix accumulation and portal tract remodeling via Spp1+ macrophages. This study highlights how altered blood flow induces fibrosis, and its potential role in decompensation, and identifies therapeutic targets for advanced liver disease.
A Temporal and Spatial Atlas of Adaptive Immune Responses in the Lymph Node Following Viral Infection
Authors: Jiang Shaowen , Mantri Madhav , Maymi Viviana , Leddon Scott A. , Schweitzer Peter , Bhandari Subash , Holdener Chase , Ntekas Ioannis , Vollmers Christopher , Flyak Andrew I. , Fowell Deborah J. , Rudd Brian D. , De Vlaminck Iwijn
Published: February 2025

The spatial organization of adaptive immune cells within lymph nodes is critical for understanding immune responses during infection and disease. Here, we introduce AIR-SPACE, an integrative approach that combines high-resolution spatial transcriptomics with paired, high-fidelity long-read sequencing of T and B cell receptors. This method enables the simultaneous analysis of cellular transcriptomes and adaptive immune receptor (AIR) repertoires within their native spatial context. We applied AIR-SPACE to mouse popliteal lymph nodes at five distinct time points after Vaccinia virus footpad infection and constructed a comprehensive map of the developing adaptive immune response. Our analysis revealed heterogeneous activation niches, characterized by Interferon-gamma (IFN-γ) production, during the early stages of infection. At later stages, we delineated sub-anatomical structures within the germinal center (GC) and observed evidence that antibody-producing plasma cells differentiate and exit the GC through the dark zone. Furthermore, by combining clonotype data with spatial lineage tracing, we demonstrate that B cell clones are shared among multiple GCs within the same lymph node, reinforcing the concept of a dynamic, interconnected network of GCs. Overall, our study demonstrates how AIR-SPACE can be used to gain insight into the spatial dynamics of infection responses within lymphoid organs.
Heterochromatin fidelity is a therapeutic vulnerability in lymphoma and other human cancers
Authors: Najia Mohamad Ali , Jha Deepak K. , Zhang Cheng , Laurent Benoit , Kubaczka Caroline , Markel Arianna , Li Christopher , Morris Vivian , Tompkins Allison , Hensch Luca , Qin Yue , Chapuy Bjoern , Huang Yu-Chung , Morse Michael , Marunde Matthew R. , Vaidya Anup , Gillespie Zachary B. , Howard Sarah A. , North Trista E. , Dominguez Daniel , Keogh Michael-Christopher , Schlaeger Thorsten M. , Shi Yang , Li Hu , Shipp Margaret M. , Blainey Paul C. , Daley George Q.
Published: February 2025

Genes involved in the regulation of chromatin structure are frequently disrupted in cancer, contributing to an aberrant transcriptome and phenotypic plasticity. Yet, therapeutics targeting mutant forms of chromatin-modifying enzymes have yielded only modest clinical utility, underscoring the difficulty of targeting the epigenomic underpinnings of aberrant gene regulatory networks. Here, we sought to identify novel epigenetic vulnerabilities in diffuse large B-cell lymphoma (DLBCL). Through phenotypic screens and biochemical analysis, we demonstrated that inhibition of the H3K9 demethylases KDM4A and KDM4C elicits potent, subtype-agnostic cytotoxicity by antagonizing transcriptional networks associated with B-cell identity and epigenetically rewiring heterochromatin. KDM4 demethylases associated with the KRAB zinc finger ZNF587, and their enzymatic inhibition led to DNA replication stress and DNA damage-induced cGAS-STING activation. Broad surveys of transcriptional data from patients also revealed KDM4 family dysregulation in several other cancer types. To explore this potential therapeutic avenue, we performed high-throughput small molecule screens with H3K9me3 nucleosome substrates and identified novel KDM4 demethylase inhibitors. AI-guided protein-ligand binding predictions suggested diverse modes of action for various small molecule hits. Our findings underscore the relevance of targeting fundamental transcriptional and epigenetic mechanisms for anti-cancer therapy.

HIGHLIGHTS

Phenotypic screens identified JIB-04 as a potent anti-cancer agent for multiple subtypes of diffuse large B-cell lymphoma

JIB-04 binds and inhibits KDM4 demethylases resulting in epigenomic rewiring of heterochromatin

KDM4 demethylases cooperate with KRAB zinc fingers to limit DNA replication stress, and KDM4 inhibition instigates DNA-damage and cGAS-STING activation in several human cancers

High-throughput small molecule screens with semi-synthetic nucleosome substrates and AI-guided molecular docking simulations identify novel KDM4 inhibitors
PROTRIDER: Protein abundance outlier detection from mass spectrometry-based proteomics data with a conditional autoencoder
Authors: Scheller Ines F. , Klaproth-Andrade Daniela , Loipfinger Stefan , Mertes Christian , Smirnov Dmitrii , Prokisch Holger , Yépez Vicente A. , Gagneur Julien
Published: February 2025

Structured abstract

Motivation

Detection of gene regulatory aberrations enhances our ability to interpret the impact of inherited and acquired genetic variation for rare disease diagnostics and tumor characterization. While numerous methods for calling RNA expression outliers from RNA-sequencing data have been proposed, the establishment of protein expression outliers from mass spectrometry data is lacking.

Results

Here we propose and assess various modeling approaches to call protein expression outliers across three datasets from rare disease diagnostics and oncology. We use as independent evidence the enrichment for outlier calls in matched RNA-seq samples and the enrichment for rare variants likely disrupting protein expression. We show that controlling for hidden confounders and technical covariates is largely beneficial and can be achieved using conditional autoencoders. Moreover, we find that the differences between experimental and fitted log-transformed intensities by such models exhibit heavy tails that are poorly captured with the Gaussian distribution and report stronger statistical calibration when instead using the Student’s t-distribution. Our resulting method, PROTRIDER, outperformed baseline approaches based on raw log-intensities Z-scores or on differential expression analysis with limma. The application of PROTRIDER reveals significant enrichments of AlphaMissense pathogenic variants in protein expression outliers. Overall, PROTRIDER provides a method to confidently identify aberrantly expressed proteins applicable to rare disease diagnostics and cancer proteomics.

Availability and Implementation

PROTRIDER is freely available atgithub.com/gagneurlab/PROTRIDER.

Contact

Julien Gagneur: gagneur at in.tum.de