bluuebunny/crossref_metadata_2025 huggingface dataset:
The One Health approach to Strongyloides stercoralis
Authors: Lyu Jiayin , Fu Xiaoyin , Liu Dengyu
Published: January 2025

The One Health concept systematically considers the health of humans, animals and the environment, emphasizing population and ecosystem health based on individual health. Strongyloides stercoralis is a soil-transmitted opportunistic pathogenic parasite that can cause strongyloidiasis in both humans and animals, potentially leading to severe disease or even death in immunocompromised hosts. This article outlines the epidemiological status, diagnosis and treatment methods of strongyloidiasis. It also discusses effective response strategies based on the One Health approach to actively cope with the zoonotic risk of S. stercoralis and promote human health development.
EU antitrust law’s resilience: the good, the bad, and the ugly
Authors: Kalintiri Andriani
Published: January 2025

Is European Union (EU) antitrust law resilient in the face of change? This question has come into the spotlight amidst the many crises and disruptions of recent times, such as COVID-19, climate change, and digitalization. This article contributes to knowledge by developing a conceptual and analytical framework for understanding and assessing legal resilience and by applying it to Articles 101 and 102 TFEU with a view to investigating their resilience in a methodologically rigorous manner. As the analysis demonstrates, the legal resilience framework has descriptive and explanatory value and its application to EU antitrust law yields two important conclusions. On the one hand, the current regime is clearly not unable to deal with change, crises, and disruptions, and claims to this effect would be unfounded. On the other hand, EU antitrust law might struggle to embrace epistemic developments and address problems in circumstances of uncertainty and complexity, at least not without its predictability, coherence, and legitimacy becoming undermined. With these lessons in mind, the article considers how EU antitrust law’s resilience may be strengthened and offers various recommendations, taking into account ongoing policy initiatives and the recently published Draghi Report.
Sleep, Pain Catastrophizing, and Pain Intensity in Treatment Seeking Adults With Opioid Use Disorder
Authors: Ault Abagail , Wilkerson Allison K. , McCauley Jenna L. , Muzzy Wendy , Mappin Georgia M. , Yonce Shayla , Barth Kelly S. , Brady Kathleen T. , George Mark S. , Wedin Sharlene , Christon Lillian M. , Flanagan Julianne C. , Yates-Johnson Anjinetta , Tutek Joshua , Lin Tao , Uhde Thomas W. , Borckardt Jeffrey J.
Published: January 2025

Objectives:

Opioid use disorder (OUD) is a large, growing, and difficult-to-treat problem. It has been associated with poor sleep, which has a relationship of mutual exacerbation with pain. These interrelationships have prompted interest in how pain catastrophizing (pain-related distortions of cognition), interacts with pain and sleep quality and quantity in those with OUD.

Methods:

Participants with chronic pain and OUD (N = 105) completed a battery of self-report assessments. A subset of these participants (N = 63) wore an actigraphy watch for 2 weeks. Six mediation models were evaluated in this cross-sectional study interrelating pain intensity, pain catastrophizing, and sleep in previously published work were run 3 times each, measuring global sleep quality through the Pittsburgh Sleep Quality Index, self-reported total sleep time (TST) through Pittsburgh Sleep Quality Index, and objective TST through actigraphy.

Results:

Three models yielded statistically significant results: (1) the relationship between global sleep quality and pain intensity mediated by pain catastrophizing (z = −2.00, P = 0.045), (2) the relationship between objective TST and pain intensity mediated by pain catastrophizing (z = −2.15, P = 0.032), and (3) the relationship between pain intensity and objective TST mediated by pain catastrophizing (z = −2.36, P = 0.018).

Conclusion:

Pain catastrophizing is a significant mediator of the relationship between the mutually exacerbating factors of sleep quality and pain intensity, and is, therefore, an important treatment target in this population. In addition, objective TST and self-reported TST were only moderately correlated and behaved differently in mediation models, suggesting that more research is needed to understand the relationship between perceived sleep quality and sleep quantity.
Comparison between unilateral and bilateral clubfoot treated with Ponseti method at walking age: static and dynamic assessment
Authors: Sapienza Marco , Testa Gianluca , Vescio Andrea , Scuderi Beatrice , de Cristo Claudia , Lucenti Ludovico , Vaccalluzzo Marco Simone , Caldaci Alessia , Canavese Federico , Pavone Vito
Published: January 2025

This study evaluated the static, postural, dynamic, and clinical outcomes among five groups of patients: a bilateral CTEV (congenital talipes equinovarus) group treated with tenotomy (n = 14), bilateral CTEV group treated conservatively (n = 6), unilateral CTEV group treated with tenotomy (n = 7), unilateral CTEV group treated conservatively (n = 3), and control group (n = 20). Data were collected through baropodometric examinations and clinical evaluations using Pirani, clubfoot assessment protocol, foot and ankle disability index (FADI), and American Orthopedic Foot and Ankle Society scores. Bilateral CTEV patients treated with tenotomy showed no statistically significant differences compared to healthy controls. Significant differences were found in lateral-lateral variation in the bilateral postural group (P = 0.002) and in static peak pressure in unilateral tenotomy patients (P = 0.046). Dynamic comparisons revealed significant differences in mean pressure between unilateral groups (P = 0.002) and lateral-lateral variation in bilateral groups (P = 0.004). The Pirani score showed significant differences between tenotomy-treated and postural patients (P = 0.000). Statistically significant differences in FADI scores were found between bilateral groups (P = 0.0037), between tenotomy-treated groups (P = 0.0020), and between the bilateral tenotomy-treated group and the unilateral postural group (P = 0.021). Bilateral CTEV patients treated with tenotomy develop static and dynamic values comparable to healthy controls. Bilateral patients develop better dynamic values compared to patients with a unilateral variant.

Level of evidence: III.
Heart failure with preserved ejection fraction: from echocardiographic characteristics to a cardiovascular damage score in a high-risk hypertensive population
Authors: Leone Dario , Vallelonga Fabrizio , Botta Matteo , Cesareo Marco , Airale Lorenzo , Colomba Anna , Fragapani Salvatore , Bruno Giulia , Mingrone Giulia , Ligato Jacopo , Sanapo Martina , Veglio Franco , Milan Alberto
Published: January 2025

Background:

Heart failure with preserved ejection fraction (HFpEF) is a high prevalence condition, with high rates of hospitalization and mortality. Arterial hypertension is the main risk factor for HFpEF. Among hypertensive patients, alterations in cardiac and vascular morphology identify hypertension-mediated organ damage (HMOD). Cardiac HMOD in terms of ventricular hypertrophy and diastolic dysfunction is a continuum between the preclinical condition (arterial hypertension) and HFpEF. In hypertensive patients, it is currently unknown what is the prevalence of individuals classifiable as being at high risk of developing HFpEF and whether aortic morphofunctional vascular changes are present.

Aim:

This study seeks to retrospectively assess the prevalence of echocardiographic alterations consistent with the diagnosis of HFpEF in a cohort of patients with essential arterial hypertension, and the prevalence of vascular HMOD (V-HMOD) in different risk categories of patients.

Methods:

Hypertensive outpatients referred at the Hypertension Center of Turin from 2003 to 2021 were retrospectively evaluated. Patients with a previous diagnosis of heart failure and known cardiovascular events were excluded. A predictive model associated with the risk of HFpEF development was calculated using echocardiographic variables. V-HMOD morphological and functional parameters were assessed by ascending aorta diameter and arterial stiffness (carotid–femoral pulse wave velocity, cfPWV).

Results:

Eight hundred and four patients (34.8% women) were analyzed, age 53.1 ± 14 years; left ventricular mass index (LVMi) and E/e′ ratio were impaired in 15.9 and 29.1% of cases, respectively. Dividing them into tertiles according to score: score 1 or less (30.2%); score 2–3 (47.4%); score at least 3 (22.7%). Patients identified at high risk of HFpEF (score ≥3) had higher age, BMI and blood pressure than the other two groups (P < 0.05); they showed a significantly higher prevalence of female patients (42.3%), treatment with at least two antihypertensive drugs (40.1%), diabetes (7.1%), and dyslipidemia (28%; P < 0.05), with a larger ascending aorta diameter (35.5 ± 5.5 mm, P < 0.05) and higher cfPWV (8.8 ± 2.4 m/s, P < 0.05).

Conclusion:

At least one in five hypertensive patients, referred to an outpatient echocardiographic examination, has C-HMOD compatible with a high-risk category of HFpEF and have a significant increase in V-HMOD. This reinforces the notion that arterial hypertension and HFpEF are not two distinctly separate conditions but a continuum of pathophysiologic alterations.
Hypertension in Sri Lanka: a systematic review of prevalence, control, care delivery and challenges
Authors: Ranasinghe Priyanga , Perera Thilina , Liyanage Sandamini , Manchanayake Minura , Rupasinghe Nilushka , Webb David J.
Published: January 2025

Hypertension (HTN) is recognized as a major modifiable risk factor for cardiovascular deaths in South Asia. Our aim was to furnish a comprehensive analysis of HTN prevalence, trends, control efforts, awareness, barriers in care delivery and associated factors, based on nationally derived evidence in Sri Lanka. A systematic search of online databases (PubMed, Web of Science, Scopus), local journals and repositories yielded 6704 results, of which 106 were included. Prevalence of HTN steadily increased from 23.7% (2005–2006) to 34.8% (2021). Associated factors identified were hyperhomocysteinaemia [odds ratio (OR) 2.80], overweight/obesity (OR 2.02), perceived job stress (OR 2.20–3.02), physical inactivity (OR 2.08–2.80), salt intake more than 5 g/day (OR 2.50), smoking (OR 2.31) and waist-to-height ratio more than or equal to 0.5 (OR 2.23). Cohort studies revealed poor blood pressure control and treatment adherence among patients. Pharmacological (n = 4) and nonpharmacological (n = 6) interventional studies were few. Studies on knowledge, attitudes and practices demonstrated a lack of public awareness. Despite the high prevalence of HTN in Sri Lanka, many cases remain undiagnosed, underscoring importance of targeted screening programmes and culture-specific public health education programmes.
A case of renovascular hypertension due to polyarteritis nodosa
Authors: Ferrao Diana , Nogueira-Silva Luis , Tavares Sofia , Lima Maria J. , Almeida Jorge
Published: January 2025

In renal vasculitis, luminal narrowing can reduce blood flow and activate the renin-angiotensin-aldosterone system, causing renovascular hypertension.

We present the case of a 47-year-old man with previous intestinal tuberculosis and episodes of lumbar pain, tender erythematous nodules and arthralgias. He had grade 3 hypertension, unresponsive to treatment, with left ventricular concentric hypertrophy and chronic kidney disease. He was admitted to the ICU due to a hypertensive emergency, with acute kidney failure and a large peri-renal hematoma. The computed tomography and angiography showed bilateral renal scarring, intrarenal pseudoaneurysms and irregularities in the renal, common hepatic and mesenteric arteries, suggesting a medium-vessel vasculitis, namely polyarteritis nodosa. Cyclophosphamide and corticosteroids were started. His blood pressure was controlled, and his kidney function remained stable.

Renovascular hypertension is, in infrequent cases, caused by an inflammatory systemic disease. When this is the case, the diagnosis must be considered and appropriately addressed.
Predicting depressive symptoms and psychological distress by circulating inflammatory mediators: A 16-month prospective study in Japanese white-collar employees
Authors: Soeishi Takahiro , Nakata Akinori , Nagata Tomohisa , Akutsu Satoshi , Tondokoro Tsukumi , Inoue Yukiko , Katsumura Fumiaki , Kikunaga Kazuki
Published: January 2025

Objective

Although increasing evidence suggests that depression/distress involves inflammatory processes, its potential sex differences and the temporal directions for this association remain elusive.

Methods

We examined the temporal association between serum inflammatory mediators and depression/distress as measured by the Center for Epidemiologic Studies Depression Scale (CES-D) and the Kessler Psychological Distress Scale (K6), in non-depressed working men and women (n = 61 and 43, respectively) by a 16-month prospective design.

Results

Fully-adjusted partial correlation analyses revealed that in men, a lower IFN-γ predicted subsequent increases in CES-D and K6 scores, while a higher TNF-α predicted increased K6 scores. In women, a higher IFN-γ predicted a subsequent increase in the CES-D score. CES-D and K6 scores did not predict inflammatory mediators at follow-up.

Conclusions

The finding suggests that inflammatory activation precedes depression/distress with distinct sex differences.
The Relationship Between Longest-Held Occupation and Hand Function in Older Adults
Authors: Levinson Jaden E. , Logue Cook Rachel N. , Brown Susan H.
Published: January 2025

Objective: Hand function, an important component of daily functioning, declines with age, yet the degree to which occupation modifies such declines is largely unknown.

Methods: Older adults (≥65) completed an online cross-sectional survey containing a standardized hand function questionnaire, occupation-related questions, and demographic information. Participants were then categorized by their longest-held occupation as Blue Collar or White Collar.

Results: Hand impairments were more common in the Blue Collar group (51.5% versus 28.9%, p < 0.05). Odds ratios indicated that Blue Collar workers were 2.71 times more likely to report hand impairments in older adulthood than White Collar workers.

Conclusions: Our findings demonstrated strong associations between occupation type and hand function, underscoring the importance of implementing hand-specific preventative workplace measures and highlighting the need to consider additional risk factors for hand impairments, including occupation, during routine clinical exams.
Predictors of Ever Using Marijuana among U.S. First Responders
Authors: Testoff Addison C. , Koru-Sengul Tulay , Solle Natasha Schaefer , Vidot Denise C. , Lee David J. , Kobetz Erin N. , Caban-Martinez Alberto J.
Published: January 2025

Objective

Estimate ever using marijuana in a sample of U.S. career first responders.

Methods

Health survey cohort data collected between 2018-2024 from employed and retired U.S. first responders was analyzed for frequency of ever using marijuana. Binary logistic regression models estimated the association between ever using marijuana and first responder demographics, employment status, and risky health behaviors.

Results

Among 1,310 current/retired first responders, 15.3% reported ever using marijuana (80.0% seldom, 18.0% often, and 2.0% always). Currently employed firefighter/paramedic/EMT’s had the highest (45.5%) while Battalion/EMS/Deputy/Fire Chiefs had the lowest use (3.0%). First responders who binge drink (adjusted OR = 1.45;[95%CI:1.03-2.03];p = 0.033), former-smoker (2.42;[1.68-3.47];p < 0.001) or current-smokers (3.61;[1.01-12.93];p = 0.049), and were retired (AOR = 1.85;[1.20-2.87] were significantly more likely to report ever using marijuana.

Conclusion

Ever using marijuana was highest among those rank firefighter/paramedics/EMT and significantly associated with binge drinking, retirement and smoking behaviors.
The association between work-life conflict and mental health - A cohort study
Authors: Thorup Lotte , Sørensen Christine Leonhard Birk , Biering Karin
Published: January 2025

Objective

Mental health problems are increasing worldwide, and research has shown that it can be affected by work-life conflict (WLC). The aim of the present study is to examine the association between WLC and both stress and depressive symptoms in early adulthood.

Methods

A cross-sectional and a 4-year follow-up study was conducted using register data and questionnaire data from The West Jutland Cohort Study (VestLiv), Denmark. 1296 individuals (age 28) were included in 2017, and 679 were included in 2021. Validated scales were used to measure both WLC, stress and depressive symptoms. Linear and logistic regression were performed.

Results

An association was found between WLC and both stress and depressive symptoms in both genders.

Conclusion

It is relevant to consider WLC a contributing factor for mental health of individuals in today’s workforce.
An Atypical Case of Neonatal Alloimmune Thrombocytopenia
Authors: Mutluoglu Gülsen , De Muynck Barbara , Emonds Marie-Paule , Van Maerken Tom
Published: January 2025

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) results from maternal antibodies targeting fetal platelets during pregnancy, often causing hemorrhagic manifestations detectable antenatally or shortly after birth. We report an atypical form of FNAIT with delayed onset in a healthy, breastfed male infant who developed diffuse petechiae 2 weeks after birth due to severe thrombocytopenia. The mother was shown to be negative for the human platelet antigen-1a (HPA-1a) allele but had anti-HPA-1a IgG antibodies, while the father and newborn were HPA-1a positive, confirming the diagnosis. Despite intravenous immunoglobulins and platelet transfusions, the recovery was slow. Analysis of breast milk demonstrated the presence of anti-HPA-1a IgG antibodies. The unusual clinical presentation 2 weeks after birth and the slow platelet recovery under appropriate treatment suggest postnatal transfer of maternal anti-HPA-1a antibodies or B lymphocytes producing these antibodies to the newborn, which may possibly have occurred through breastfeeding. Further research is needed to validate these findings and understand the role of breast milk in provoking the disease. Early detection and management remain essential to prevent serious complications associated with FNAIT.
Comparison of Capizzi and High-dose Methotrexate Approaches in the Treatment of Pediatric B-cell Acute Lymphoblastic Leukemia
Authors: Yalcin Gungoren Ezgi , Koc Basak , Zulfikar Bulent
Published: January 2025

Childhood cancers, with leukemia at the forefront, comprise 97% acute leukemia and 3% chronic leukemia, with 75% of acute leukemias being of lymphoblastic origin. Over the past 50 years, survival rates have witnessed a remarkable increase, progressing from around 10% to achieving cure rates exceeding 90% in certain childhood ALL subgroups with the advent of combined therapies. Between 1999 and 2018, a total of 123 patients diagnosed with B-ALL were initially identified, but after applying exclusion criteria, 105 patients were included in the evaluation, who were treated with COG protocols at our center. The mean follow-up duration for patients was determined to be a median of 74 months (min to max: 2 to 228 months). When the cases were evaluated at the end of the study, 59 of 59 individuals in the standard risk group (100%), 21 of 26 individuals in the high-risk group (80.7%), and 14 of 20 individuals in the very high group (70%) were alive. Patients were categorized into 4 groups based on the methotrexate (MTX) doses they received during Phase 3 and Phase 5 of treatment. Event-free survival and overall survival were evaluated among these groups. It was observed that patients in the standard-risk group had significantly higher event-free and overall survival rates. However, no significant difference was found in survival rates when evaluated based on the treatment groups each risk group received by the patients.
Topical review: Ocular surface abnormalities in neurodegenerative disorders
Authors: Waller Sophie E. , Stockwell Joseph B. , Fung Victor S. C. , Anstey Kaarin J. , Colebatch James G. , Markoulli Maria , Krishnan Arun V.
Published: January 2025

SIGNIFICANCE

In an aging population, the number of people living with neurodegenerative disease is projected to increase. It is vital to develop reliable, noninvasive biomarkers to detect disease onset and monitor progression, and there is a growing body of research into the ocular surface as a potential source of such biomarkers.

BACKGROUND

This article reviews the potential of in vivo corneal confocal microscopy and tear fluid analysis as tools for biomarker development. Corneal confocal microscopy, traditionally used for studying corneal health, offers high-resolution imaging of corneal nerves and has shown promise for examining systemic diseases such as Alzheimer disease and Parkinson's disease. Complementarily, tear fluid analysis, known for its ease of collection, reflects systemic changes in neurodegenerative conditions.

CONCLUSION

Together, these noninvasive techniques provide insights into disease onset and progression and hold potential for advancing diagnostic and treatment strategies.
Overexpression of MAGE-A2 is Related to the Malignant Degree and Progression of Disease in Patients With Clear Cell Renal Cell Carcinoma
Authors: Mohsenzadegan Monireh , Fattahi Fahimeh , Kalantari Elham , Abolhasani Maryam , Madjd Zahra , Saeednejad Zanjani Leili
Published: January 2025

Melanoma antigen gene-A2 (MAGE-A2) is one of the most cancer-testis antigens overexpressed in a variety of malignancies. However, the expression of MAGE-A2 for clinical values in the pathophysiology of renal cell carcinoma (RCC) is unknown. For the first time, the present study was conducted to examine the expression and prognostic significance of MAGE-A2 expression in clear cell RCC (ccRCC). MAGE-A2 expression was assayed in 162 well-defined ccRCC samples using immunohistochemistry staining on tissue microarrays. The association between MAGE-A2 expression and clinic-pathologic features as well as survival outcomes were then performed. A significant and positive correlation was found between cytoplasmic expression of MAGE-A2 with tumor size (P=0.008), nucleolar grade (P =0.001), tumor stage (P =0.001), microvascular invasion (P=0.001), invasion to renal pelvis (P=0.032), renal sinus fat (P=0.004), and Gerota’s fascia (P=0.028) as well as histologic tumor necrosis (P<0.0001). Increased expression of MAGE-A2 was observed to be associated with shorter progression-free survival (PFS) compared with patients with low expression of MAGE-A2 (P=0.032). Multivariate analysis revealed that tumor size and nucleolar grade are independent predictors of the PFS (P=0.054, P=0.032, respectively). Our results indicated that increased cytoplasmic expression of MAGE-A2 is associated with the malignant degree and progression of ccRCC. This data improved the significance of MAGE-A2 expression and will potentially allow using MAGE-A2 for the prognosis of the disease and immunotherapy in patients with ccRCC.
Health-related Quality of Life and Exercise Capacity in Double Lung Transplant Recipients With Baseline Lung Allograft Dysfunction
Authors: Rullay Alisha , Kaur Karina , Holman Jennifer , van den Bosch Laura C. , Weinkauf Justin G. , Nagendran Jayan , Varughese Rhea A. , Hirji Alim S. , Lien Dale C. , Weatherald Jason C. , Halloran Kieran M.
Published: January 2025

Background.

Baseline lung allograft dysfunction (BLAD) after lung transplant is associated with an increased risk of dying, but the association with health-related quality of life (HRQL) and exercise capacity is not known. We hypothesized that BLAD would be associated with reduced HRQL and 6-min walk distance (6MWD) at 1 y post–lung transplant.

Methods.

We analyzed patients who underwent lung transplants in our program from 2004 to 2018 who completed 1-y 36-item Short Form (SF-36) questionnaire and 6MWD testing. We secondarily analyzed the Beck Depression Inventory and Borg dyspnea scores in patients using the available data. We defined BLAD as a failure of both forced expiratory volume in 1 s and forced vital capacity to reach ≥80% predicted of a healthy reference population’s lung function on 2 consecutive tests ≥3 wk apart at any time point posttransplant. We tested the relationship between BLAD status and SF-36 physical component summaries and 6MWD using least squares regression, adjusting for age at transplant, sex at birth, and primary lung disease.

Results.

Two hundred sixty-four patients were included, 96 (36%) of whom met the criteria for BLAD. Patients with interstitial lung disease as an indication for transplant and those who received older, female, and heavy smoking donors were at increased risk of BLAD. SF-36 physical component summary scores were lower in patients with BLAD (75 versus 85; P = 0.0076), as were 6MWD values (528 versus 572 m; P = 0.0053). BLAD was associated with lower SF-36 scores (P = 0.0025) and 6MWD (P = 0.0008) in adjusted regression models at 1 y posttransplant. We did not observe differences in Beck Depression Inventory or Borg scores.

Conclusions.

BLAD was associated with reduced HRQL and 6MWD scores at 1 y posttransplant in adjusted models. This suggests that poor posttransplant lung function could contribute to lower HRQL and exercise capacity in lung recipients and is worthy of further exploration in terms of causes, prevention, and treatment.
Impact of Granulocyte Colony-Stimulating Factor (G-CSF) on Clinical Outcomes in Allogeneic Hematopoietic Cell Transplantation: Does Speeding Up Neutrophil Engraftment Make a Difference?
Authors: Alnughmush Ahmed , Sayyed Ayman , Remberger Mats , AL-Shaibani Eshrak , Chen Carol , Chiarello Caden , Pasic Ivan , Novitzky-Basso Igor , Law Arjun Datt , Lam Wilson , Kim Dennis (Dong Hwan) , Gerbitz Armin , Viswabandya Auro , Kumar Rajat , Michelis Fotios V. , Mattsson Jonas
Published: January 2025

Background.

Despite decades of post–allogeneic hematopoietic cell transplantation (HCT) growth factor utilization, its role remains undefined, leading to ongoing debates and research. The theoretical impacts of growth factors have been challenged in numerous studies.

Methods.

In this retrospective cohort study conducted at the Princess Margaret Cancer Centre, we analyzed the clinical outcomes of 509 patients who underwent allogeneic HCT between May 1, 2019, and May 31, 2022. This study aimed to assess the impact of granulocyte colony-stimulating factor (G-CSF) administration posttransplantation on neutrophil and platelet engraftment, incidence of bloodstream infections (BSIs), graft-versus-host disease, engraftment syndrome (ES), and survival metrics including overall survival, nonrelapse mortality, and graft-versus-host disease–free/relapse-free survival.

Results.

Our findings indicate that G-CSF administration expedited neutrophil engraftment (16 versus 18 d, P = 0.009) and was associated with a decreased incidence of BSI (9.4% versus 31.3%, P = 0.014). However, this benefit was counterbalanced by a significant delay in platelet engraftment (21 versus 17 d, P < 0.001). Multivariate logistic regression analysis identified mismatched donors (odds ratio, 1.72; 95% confidence interval, 1.03-2.88; P = 0.038) and the duration of G-CSF therapy (odds ratio, 1.04; 95% confidence interval, 1.00-1.09; P = 0.038) as independent predictors for the development of ES. Despite these hematological impacts, there was no observed advantage in overall survival, nonrelapse mortality, or graft-versus-host disease–free/relapse-free survival among patients who received G-CSF compared with those who did not.

Conclusions.

Although G-CSF post-HCT expedited neutrophil engraftment and reduced BSI risk, it did not result in a survival advantage. The association with ES necessitates careful consideration.
Autoimmune Encephalitis in Catatonic and Treatment-Resistant Psychotic Patients Referred to Electroconvulsive Therapy
Authors: Beatino Maria Francesca , Weiss Francesco , Torrigiani Samuele , Caruso Valerio , Elefante Camilla , Medda Pierpaolo , Brancati Giulio Emilio , Perugi Giulio
Published: January 2025

Autoimmune encephalitis (AE) tends to manifest as a mixture of neuropsychiatric and somatic symptoms, either of which may predominate, and often shows a progressive clinical course sometimes leading to life-threatening conditions. Catatonic and psychotic syndromes, regardless of whether associated with dysautonomia, are common manifestations of AE, especially concerning the anti-NMDAR subtype. Several autoantibodies targeting different neuronal epitopes have been linked to specific clinical manifestations and their detection is embedded in some of the diagnostic criteria for AE. Therapeutical management of AE is challenged by limited diagnostic abilities and poor understanding of the underlying pathophysiology for most of its subtypes. Although the prompt delivery of disease-modifying therapies represents the cornerstone of treatment and primarily affects prognosis, less is known about the role of symptom specific supportive measures like electroconvulsive therapy (ECT). Based on a systematic review of 26 patient-level descriptions of individuals, each with a diagnosis of AE treated with ECT, a favorable clinical response was found in more than ¾ of the revised cases (76.9%). The most common indications for ECT administration were catatonic and psychotic syndromes, often nonresponsive to prior pharmacotherapy with benzodiazepines, antipsychotic, and other psychotropic drugs. Noteworthy side effects were only reported for 3 of 26 patients. Though the low number of cases and publication bias should be considered as major limitations, current available reports are in support of the inclusion of ECT in the integrated therapeutic algorithm of AE to address psychiatric conditions such as severe psychosis and catatonia.
Use of Electroconvulsive Therapy Treatment in Adolescents in Singapore
Authors: Chen Birong , Fu Yuqian , Li Ziqiang , Tan Xiaowei , Li Juanjuan , Herrera Manoza Michaela , Koh Doris Sok Hian , Tor Phern Chern
Published: January 2025

Background

Electroconvulsive therapy (ECT) is a highly effective treatment for schizophrenia and mood disorders; however, most evidence is derived from the adult population, with less evidence in adolescents. We sought to determine the use of ECT in adolescents in the Institute of Mental Health (IMH) and evaluate the treatment outcome.

Methods

We conducted a retrospective naturalistic analysis of ECT registry data of patients aged from 10 to 19 years from March 2017 to March 2023. Descriptive analysis was used to analyze the demographics and clinical characteristics. Paired t tests were used to compare the change in clinical outcome scores, including the Brief Psychiatric Rating Scale (BPRS), Montgomery-Asberg Depression Rating Scale (MADRS), Clinical Global Impressions Scale — Severity (CGI-S), and Montreal Cognitive Assessment (MoCA) before and after 2 weeks of ECT treatment.

Results

Fifty-five patients were included for analysis. There was a significant improvement in BPRS (P < 0.001), MADRS (P = 0.005), and CGI-S (P < 0.001), and the average CGI-I score was 2.275 (SD, 0.81), which is equivalent to “much improved” after 6 sessions of treatment. Of all patients, 48.5% showed significant clinical improvement. There was no significant change in MoCA scores (P = 0.218).

Conclusions

Our preliminary findings show that ECT is a safe, rapid, and effective treatment for psychotic and mood disorders in adolescents. Further studies with a larger sample size and specific subgroup analysis are needed to establish the effectiveness of ECT and identify predictors of response in this population.
ZapA employs a two-pronged mechanism to facilitate Z ring formation inEscherichia coli
Authors: Cui Yuanyuan , Gong Han , Yan Di , Li Hao , Yang Wenjie , Li Ying , Chen Xiangdong , Lutkenhaus Joe , Huang Sheng-You , Yang Xinxing , Du Shishen
Published: January 2025

The tubulin-like protein FtsZ assembles into the Z ring which leads to the assembly and activation of the division machinery in most bacteria. ZapA, a widely conserved protein that interacts with FtsZ, plays a pivotal role in organizing FtsZ filaments into a coherent Z ring. Previous studies revealed that ZapA forms a dumbbell-like tetramer that binds cooperatively to FtsZ filaments and aligns them in parallel, leading to the straightening and organization of FtsZ filament bundles. However, how ZapA interacts with FtsZ remains obscure. In this study, we uncover how ZapA interacts with FtsZ to facilitate Z ring formation inEscherichia coli. We find that mutations affecting surface exposed residues at the junction between adjacent FtsZ subunits in a filament as well as in an N-terminal motif of FtsZ weaken its interaction with ZapAin vivoandin vitro, indicating that ZapA binds to these regions of FtsZ. Consistent with this, ZapA prefers FtsZ polymers over monomeric FtsZ molecules and site-specific crosslinking confirmed that the dimer head domain of ZapA is in contact with the junction of FtsZ subunits. As a result, disruption of the putative interaction interfaces between FtsZ and ZapA abolishes the midcell localization of ZapA. Taken together, our results suggest that ZapA tetramers grab the N-terminal tails of FtsZ and then bind to the junctions between FtsZ subunits in the filament to straighten and crosslink parallel FtsZ filaments into the Z ring.

Significance

ZapA is a widely conserved FtsZ-associated protein that promotes the organization of the Z ring, the key cytoskeletal element in the bacterial divisome. Although ZapA is known to crosslink FtsZ filaments, how it interacts with FtsZ remains enigmatic. In this study, we find thatE. coliZapA utilizes a dual binding mode in which it binds the junction between FtsZ subunits in a filament and to an N-terminal motif in FtsZ so that it can straighten and crosslink parallel FtsZ filaments simultaneously. Since the junction is formed when FtsZ polymerizes and falls apart when FtsZ depolymerizes, this interaction mode indicates that ZapA employs the polymerization dynamics of FtsZ to organize the filaments into the Z ring.
Massive culture-based approach for the screening of AmpC-, ESBL- and carbapenemase producers from complex samples
Authors: Taddeucci-Rocha Gabriel , de Oliveira Costa Victoria , da Silva Sarah Vitória Martins , Gonçalves Jéssica Britto , da Silva Natalia Chilinque Zambão , Garnica Marcia Maiolino , Picão Renata Cristina
Published: January 2025

ABSTRACT

Gram-negative bacilli producing beta-lactamases are major causes of difficult-to-treat infections, especially the AmpC, ESBL, and carbapenemase types. Their spread within and outside hospital settings demands effective detection and monitoring in various environments, but current methods for this purpose often neglect important groups of beta-lactamases or are expensive and time consuming. We aimed to develop and test a massive culture approach to detect and differentiate between beta-lactamase producers from complex samples. The method involved an enrichment step on MacConkey agar supplemented with ceftriaxone to select for AmpC, ESBL, and carbapenemase producers, followed by replica plating under selective pressures (cefoxitin, cefepime, imipenem) to differentiate them. The massive culture approach effectively differentiated strains producing different beta-lactamases in mixed cultures. In tests with rectal swabs, our method demonstrated 100% sensitivity, higher specificity, and greater accuracy for ESBL detection compared to the reference method. Additionally, it identified a broader spectrum of beta-lactamase producers, including AmpC and carbapenemase. The massive culture approach is a promising tool for detecting and differentiating gram-negative bacilli producing beta-lactamases from rectal swabs. Due to the additional time required to produce results, this method is most suitable for central and research laboratories and enhances surveillance capabilities for antimicrobial resistance.

IMPORTANCE

The dissemination of multidrug-resistant bacteria producing beta-lactamases in healthcare and community settings demands effective detection and monitoring. Existing methods may miss key beta-lactamase groups or are costly and time-consuming. In this study, a comprehensive culture-based approach using replica plating was developed and used to detect and differentiate beta-lactamase producers from rectal swabs. It showed higher specificity and greater accuracy for ESBL detection compared to the reference method, while identifying a broader range of beta-lactamase producers, including AmpC and carbapenemase. Despite requiring additional processing time, this method is suitable for central and research laboratories, enhancing antimicrobial resistance surveillance.
The subunit 3 of the SUPERKILLER (SKI) complex mediates miR172-directed cleavage ofNodule Number Control 1(NNC1) to modulate nodulation inMedicagotruncatula
Authors: Traubenik Soledad , Reynoso Mauricio Alberto , Sánchez-Rodríguez Francisco , Yacullo Milagros , Christ Aurelie , Hummel Maureen , Blein Thomas , Crespi Martín , Bailey-Serres Julia , Blanco Flavio Antonio , Zanetti María Eugenia
Published: January 2025

Legumes and rhizobia establish a nitrogen-fixing symbiosis that involves the formation of a lateral root organ, the nodule, and the infection process that allows intracellular accommodation of rhizobia within nodule cells. This process involves significant gene expression changes regulated at the transcriptional and post-transcriptional levels. We have previously shown that a transcript encoding the subunit 3 of the Superkiller Complex (SKI), which guides mRNAs to the exosome for 3′-to-5′ degradation, is required for nodule formation and bacterial persistence within the nodule, as well as the induction of early nodulation genes (e.g.,MtENOD40) during theMedicago truncatula-Sinorhizobium melilotisymbiosis. Here, we reveal through transcript degradome and small RNA sequencing analysis that knockdown ofMtSKI3impairs the miR172-directed endonucleolytic cleavage of the mRNA encoding Nodule Number Control 1 (MtNNC1), an APETALA2 transcription factor that negatively modulates nodulation. Knockdown ofMtNNC1enhances nodule number, bacterial infection, and the induction ofMtENOD40upon inoculation withS. melilotiwhereas overexpression of a miR172-resistant form ofMtNNC1significantly reduces nodule formation. This work identifies miR172 cleavage ofMtNNC1and its control by MtSKI3, a component of the 3′-to-5′mRNA degradation pathway, as a new regulatory hub controlling indeterminate nodulation.
Disentangling phonology from phonological short-term memory in Alzheimer’s disease phenotypes
Authors: Henderson Shalom K. , Halai Ajay , Tsvetanov Kamen A. , Cope Thomas E. , Patterson Karalyn E. , Rowe James B. , Lambon Ralph Matthew A.
Published: January 2025

Impaired phonological short-term memory is a core feature of the logopenic variant of primary progressive aphasia (lvPPA), but it is not clear whether a core phonological processing deficit is also present. We asked three questions: (i) beyond short-term memory impairment, do people with lvPPA have an impairment within phonology itself?; (ii) is their performance in working memory and confrontation naming reflective of this phonological impairment and/or other key contributing deficits (e.g., semantic)?; and (iii) is their repetition performance related to structural and functional differences in key language-dominant regions? We compared non- word and word repetition and short-term memory performance in patients with typical, amnestic Alzheimer’s disease (tAD,n= 9), lvPPA per consensus criteria (n= 10), and others who previously satisfied definitions of lvPPA but had progressed with multi-domain cognitive impairments (lvPPA+,n= 8). Bayesian analyses revealed no group differences in phonological tasks of word and non-word repetition. There was, however, a very strong group effect on multi-syllabic word/phrase repetition. We found very strong evidence for an effect of self- reported hearing loss on both word and non-word repetition, but not multi-syllabic word/phrase repetition. A comparison of phonological (as indexed by non-word repetition)versusworking memory (as measured by multisyllabic word repetition and digit span) and confrontation naming tasks produced either no evidence or evidence for no correlation. Confrontation naming correlated positively with multisyllabic word/phrase repetition and semantic assessments across the whole group. Beyond the expected grey matter reductions in patients relative to controls in the left posterior superior temporal gyrus, anterior temporal lobe, and inferior temporal gyrus, we found no evidence for the associations between non-word repetition and functional connectivity between all regions of interest in the whole group. When excluding controls, the only anecdotal evidence that was corroborated by frequentist multiple regression was for an association between non-word repetition and functional connectivity between dorsal premotor and posterior superior temporal gyrus after controlling for the grey matter volumes in these regions. We have shown that deficits in “pure” phonological tasks, namely single word and non-word repetition, are (i) not dependent on working memory and (ii) greater in patients with a self-reported hearing loss across all groups with lvPPA or tAD. Our results suggest that instead of having a core phonological impairment, lvPPA patients have a working memory/buffering impairment that adversely affects their performance on length-dependent working memory tasks.
A tightly regulated auxin signaling landscape is required for spatial accommodation of lateral roots inArabidopsis
Authors: Bùi Thái X. , Shekhar Vinay , Marc-Martin Sophie , Bellande Kevin , Vermeer Joop E.M.
Published: January 2025

InArabidopsis thaliana, lateral root (LR) development requires spatial accommodation responses in overlying endodermal cells. This includes loss of cell volume whilst maintaining membrane integrity to allow the expansion of the underlying LR primordia (LRPs). These accommodation responses are regulated by auxin-mediated signaling, specifically through Aux/IAA proteins, involvingIAA3/SHY2. Plants that express a stabilized version of SHY2, shy2-2, in differentiated endodermal cells,CASP1pro::shy2-2plants, fail to make LRs. Exogenous treatment with 1- naphthaleneacetic acid (NAA) was reported to partially restore LR formation in this spatial accommodation mutant. Using treatments with auxins with different transport properties, such as NAA, indole-3-acetic acid (IAA), and 2,4-dichlorophenoxyacetic acid (2,4-D), we assessed the ability of each auxin to rescue LR formation inCASP1pro::shy2-2roots. This revealed that IAA is the most effective in partially restoring LR development, NAA is effective in inducing LRPs but cannot maintain their canonical phenotype, whereas 2,4-D induces non-controlled cell divisions. In addition, we show that inCASP1pro::shy2-2 roots,AUX1appears to be repressed in the zone where oscillation of the auxin response have been described. Our study advances the understanding of auxin-regulated spatial accommodation mechanisms during LRP formation and highlights the complex interplay of auxin transport and signaling in bypassing the endodermal constraints.
Ancient gene clusters initiate monoterpenoid indole alkaloid biosynthesis and C3 stereochemistry inversion
Authors: Hwang Jaewook , Kirshner Jonathan , Ramey Deschênes Daniel André , Richardson Matthew Bailey , Fleck Steven J. , Guo Jun , Perley Jacob Owen , Shahsavarani Mohammadamin , Garza-Garcia Jorge Jonathan Oswaldo , Seveck Alyssa Dawn , Doiron Savannah Sadie , Mai Zhan , Silliphant Stephen Nelson , Calhoun Larry , Gao Di , Lian Jiazhang , Deslongchamps Ghislain , Albert Victor A. , Qu Yang
Published: January 2025

The inversion of C3 stereochemistry in monoterpenoid indole alkaloids (MIAs), derived from the central precursor strictosidine (3S), is essential for synthesizing numerous 3RMIAs and oxindoles, including the antihypertensive drug reserpine found inRauvolfia serpentina(Indian snakeroot) andRauvolfia tetraphylla(devil pepper) of the plant family Apocynaceae. MIA biosynthesis begins with the reduction of strictosidine aglycone by various reductases, preserving the initial 3Sstereochemistry. In this study, we identify and biochemically characterize a conserved oxidase-reductase pair from the Apocynaceae, Rubiaceae, and Gelsemiaceae families of the order Gentianales: the heteroyohimbine/yohimbine/corynanthe C3-oxidase (HYC3O) and C3-reductase (HYC3R). These enzymes collaboratively invert the 3Sstereochemistry to 3Racross a range of substrates, resolving the long-standing question about the origin of 3RMIAs and oxindole derivatives, and facilitation of reserpine biosynthesis. Notably,HYC3OandHYC3Rare located within gene clusters in both theR. tetraphyllaandCatharanthus roseus(Madagascar periwinkle) genomes, which are partially homologous to an elusive geissoschizine synthase (GS) gene cluster we also identified in these species. InR. tetraphylla, these clusters occur closely in tandem on a single chromosome, likely stemming from a single segmental duplication event, while inC. roseus, a closely related member of rauvolfioid Apocynaceae, they were later separated by a chromosomal translocation. The ancestral genomic context for both clusters can be traced all the way back to common ancestry with grapevine. Given the presence of syntenic GS homologs inMitragyna speciosa(Rubiaceae), the GS cluster, at least in part, probably evolved at the base of the Gentianales, which split from other core eudicots up to 135 million years ago. We also show that the strictosidine biosynthetic gene cluster, required to initiate the MIA pathway, plausibly evolved concurrently. The reserpine biosynthetic cluster likely arose much later in the rauvolfioid lineage of Apocynaceae. Collectively, our work uncovers the genomic and biochemical basis for key events in MIA evolution and diversification, providing insights beyond the well-characterized vinblastine and ajmaline biosynthetic pathways.
Star-Shaped Glatiramer Acetate Mitigates Pulmonary Dysfunction and Brain Neurodegeneration in a Murine Model of Cryptococcus-Associated IRIS
Authors: Anwar Shehata , Zhou Jinyan , Kowalski Lauren , Saylor Joshua , Shukla Devanshi , Boetel Katelyn , Song Ziyuan , Sharma Kamal , Cheng Jianjun , Inoue Makoto
Published: January 2025

Cryptococcal-associated immune reconstitution inflammatory syndrome (C-IRIS) is a clinical worsening or new presentation of cryptococcal disease following the initiation of antiretroviral therapy. C-IRIS is primarily driven by an influx of pathological CD4+T cells, which triggers a hyperinflammatory response. The murine model of C-IRIS is a way to study the disease in mice and understand how the immune system triggers life-threatening outcomes in patients. We previously developed a murine C-IRIS model and demonstrated that C-IRIS is triggered by pathological CD4+T cells, particularly Th1 cells, in the brain, which triggers neurodegeneration and pulmonary dysfunction. Using this unique mouse model, we tested the therapeutic effect of a star-shaped glatiramer acetate (sGA), which is a more effective isomeric form than linear GA. Here, we observed that sGA suppresses Th1 differentiation in the lung tissues, reducing CD4+T cell and Th1 cell count. It also reduced microglia populations in the brain. Together, these changes improved respiratory dysfunction caused by C-IRIS, lowered mortality rate, and reduced brain neurodegeneration. These findings suggest that sGA could be an effective therapeutic strategy for managing C-IRIS.