bluuebunny/crossref_metadata_2025 huggingface dataset:
Beyond constructs and principles: addressing gender-related barriers to high, equitable immunization coverage
Authors: Gerber Willow , Fields Rebecca , Guesela Neide , Nuhu Khadijah A. Ibrahim , Manika Eugene
Published: April 2024

The global immunization community has only recently recognized that addressing gender-related barriers to vaccination is critical to improving equity and increasing protection against vaccine-preventable diseases. USAID's MOMENTUM Routine Immunization Transformation and Equity project aims to strengthen routine immunization programs to overcome entrenched obstacles to reaching zero-dose and under-immunized children while supporting the introduction of other new vaccines given over the life course. From the outset, the project recognized the need to mainstream gender into its global and country level work, incorporating gender considerations into all phases of the program cycle, from assessment to activity design, strategic communications, monitoring, evaluation, and continuous learning. Its gender mainstreaming efforts focus on five areas of improvement for immunization: service access and convenience; service quality and experience; communication and demand generation for immunization among caregivers (both women and men) and families; making services more responsive to agency and autonomy constraints of female caregivers; and the conditions and circumstances of health workers, who are mostly women. The authors describe approaches the project has applied to build capacity of its own global and country level staff to both recognize the gender dimensions inherent in common obstacles to immunization and ways to address them. Authors describe project activities carried out at global and country levels and share experience and challenges encountered in increasing recognition of gender barriers, moving from theory to practical action in addressing them, building capacity, and gauging the success of the work to date. The lessons learned are useful to colleagues working within the circumstances of time-limited and geography-specific projects whose main focus is to improve equity in immunization.
Omega-3 and omega-6 polyunsaturated fatty acids and their potential therapeutic role in protozoan infections
Authors: Rahman Sajid Ur , Weng Tzu-Nin , Qadeer Abdul , Nawaz Saqib , Ullah Hanif , Chen Chien-Chin
Published: April 2024

Protozoa exert a serious global threat of growing concern to human, and animal, and there is a need for the advancement of novel therapeutic strategies to effectively treat or mitigate the impact of associated diseases. Omega polyunsaturated fatty acids (ω-PUFAs), including Omega-3 (ω-3) and omega-6 (ω-6), are constituents derived from various natural sources, have gained significant attention for their therapeutic role in parasitic infections and a variety of essential structural and regulatory functions in animals and humans. Both ω-3 and ω-6 decrease the growth and survival rate of parasites through metabolized anti-inflammatory mediators, such as lipoxins, resolvins, and protectins, and have both in vivo and in vitro protective effects against various protozoan infections. The ω-PUFAs have been shown to modulate the host immune response by a commonly known mechanism such as (inhibition of arachidonic acid (AA) metabolic process, production of anti-inflammatory mediators, modification of intracellular lipids, and activation of the nuclear receptor), and promotion of a shift towards a more effective immune defense against parasitic invaders by regulation the inflammation like prostaglandins, leukotrienes, thromboxane, are involved in controlling the inflammatory reaction. The immune modulation may involve reducing inflammation, enhancing phagocytosis, and suppressing parasitic virulence factors. The unique properties of ω-PUFAs could prevent protozoan infections, representing an important area of study. This review explores the clinical impact of ω-PUFAs against some protozoan infections, elucidating possible mechanisms of action and supportive therapy for preventing various parasitic infections in humans and animals, such as toxoplasmosis, malaria, coccidiosis, and chagas disease. ω-PUFAs show promise as a therapeutic approach for parasitic infections due to their direct anti-parasitic effects and their ability to modulate the host immune response. Additionally, we discuss current treatment options and suggest perspectives for future studies. This could potentially provide an alternative or supplementary treatment option for these complex global health problems.
Case report: EBV-related eye orbits and sinuses lymphohistiocytic infiltration responsive to rituximab in a patient with X lymphoproliferative syndrome type 1
Authors: Giardino Giuliana , Lanni Vittoria , Mascolo Massimo , Russo Daniela , Cirillo Emilia , Romano Roberta , Cillo Francesca , Grilli Laura , Prencipe Maria Rosaria , Iuliano Adriana , Uccello Giovanni , De Fusco Carmela , Menna Giuseppe , Scalia Giulia , Portella Giuseppe , Pignata Claudio
Published: April 2024

Background and aims

X lymphoproliferative syndrome type 1 (XLP1) is a rare inborn error of immunity due to mutations of SH2D1A, encoding for slam-associated protein (SAP). The clinical phenotype includes severe mononucleosis, hemophagocytic lymphohistiocytosis (HLH), and B-cell lymphomas.

Methods

We report the case of a child affected with XLP1 who presented with an incomplete HLH, triggered by Epstein–Barr virus (EBV) and treated with rituximab, involving orbits and paranasal sinuses.

Results

The lesion was indistinguishable from lymphoma, complicating diagnosis and treatment. In addition, considering the high incidence of lymphoma in patients with XLP1, histology helped define its nature, driving therapeutic choices.

Conclusion

We described an unusual presentation of incomplete HLH in a patient affected with XLP1: an EBV-driven infiltration of the orbits and paranasal sinuses. This led us to a challenging differential diagnosis of lymphoma-associated hemophagocytic syndrome, which can be frequently observed in patients with XLP1. Considering the extremely poor prognosis of this clinical finding, we sought for a prompt diagnosis and managed to obtain it and to immediately establish the right treatment on the basis of the pathological finding.
Nlrp2 deletion ameliorates kidney damage in a mouse model of cystinosis
Authors: Rossi Marianna Nicoletta , Matteo Valentina , Diomedi-Camassei Francesca , De Leo Ester , Devuyst Olivier , Lamkanfi Mohamed , Caiello Ivan , Loricchio Elena , Bellomo Francesco , Taranta Anna , Emma Francesco , De Benedetti Fabrizio , Prencipe Giusi
Published: April 2024

Cystinosis is a rare autosomal recessive disorder caused by mutations in the CTNS gene that encodes cystinosin, a ubiquitous lysosomal cystine/H+ antiporter. The hallmark of the disease is progressive accumulation of cystine and cystine crystals in virtually all tissues. At the kidney level, human cystinosis is characterized by the development of renal Fanconi syndrome and progressive glomerular and interstitial damage leading to end-stage kidney disease in the second or third decade of life. The exact molecular mechanisms involved in the pathogenesis of renal disease in cystinosis are incompletely elucidated. We have previously shown upregulation of NLRP2 in human cystinotic proximal tubular epithelial cells and its role in promoting inflammatory and profibrotic responses. Herein, we have investigated the role of NLRP2 in vivo using a mouse model of cystinosis in which we have confirmed upregulation of Nlrp2 in the renal parenchyma. Our studies show that double knock out Ctns-/- Nlrp2-/- animals exhibit delayed development of Fanconi syndrome and kidney tissue damage. Specifically, we observed at 4-6 months of age that animals had less glucosuria and calciuria and markedly preserved renal tissue, as assessed by significantly lower levels of inflammatory cell infiltration, tubular atrophy, and interstitial fibrosis. Also, the mRNA expression of some inflammatory mediators (Cxcl1 and Saa1) and the rate of apoptosis were significantly decreased in 4-6-month old kidneys harvested from Ctns-/- Nlrp2-/- mice compared to those obtained from Ctns-/-mice. At 12-14 months of age, renal histological was markedly altered in both genetic models, although double KO animals had lower degree of polyuria and low molecular weight proteinuria and decreased mRNA expression levels of Il6 and Mcp1. Altogether, these data indicate that Nlrp2 is a potential pharmacological target for delaying progression of kidney disease in cystinosis.
A model for community-driven development of best practices: the Ocean Observatories Initiative Biogeochemical Sensor Data Best Practices and User Guide
Authors: Palevsky Hilary I. , Clayton Sophie , Benway Heather , Maheigan Mairead , Atamanchuk Dariia , Battisti Roman , Batryn Jennifer , Bourbonnais Annie , Briggs Ellen M. , Carvalho Filipa , Chase Alison P. , Eveleth Rachel , Fatland Rob , Fogaren Kristen E. , Fram Jonathan Peter , Hartman Susan E. , Le Bras Isabela , Manning Cara C. M. , Needoba Joseph A. , Neely Merrie Beth , Oliver Hilde , Reed Andrew C. , Rheuban Jennie E. , Schallenberg Christina , Walsh Ian , Wingard Christopher , Bauer Kohen , Chen Baoshan , Cuevas Jose , Flecha Susana , Horwith Micah , Melendez Melissa , Menz Tyler , Rivero-Calle Sara , Roden Nicholas P. , Steinhoff Tobias , Trucco-Pignata Pablo Nicolás , Vardaro Michael F. , Yoder Meg
Published: April 2024

The field of oceanography is transitioning from data-poor to data-rich, thanks in part to increased deployment of in-situ platforms and sensors, such as those that instrument the US-funded Ocean Observatories Initiative (OOI). However, generating science-ready data products from these sensors, particularly those making biogeochemical measurements, often requires extensive end-user calibration and validation procedures, which can present a significant barrier. Openly available community-developed and -vetted Best Practices contribute to overcoming such barriers, but collaboratively developing user-friendly Best Practices can be challenging. Here we describe the process undertaken by the NSF-funded OOI Biogeochemical Sensor Data Working Group to develop Best Practices for creating science-ready biogeochemical data products from OOI data, culminating in the publication of the GOOS-endorsed OOI Biogeochemical Sensor Data Best Practices and User Guide. For Best Practices related to ocean observatories, engaging observatory staff is crucial, but having a “user-defined” process ensures the final product addresses user needs. Our process prioritized bringing together a diverse team and creating an inclusive environment where all participants could effectively contribute. Incorporating the perspectives of a wide range of experts and prospective end users through an iterative review process that included “Beta Testers’’ enabled us to produce a final product that combines technical information with a user-friendly structure that illustrates data analysis pipelines via flowcharts and worked examples accompanied by pseudo-code. Our process and its impact on improving the accessibility and utility of the end product provides a roadmap for other groups undertaking similar community-driven activities to develop and disseminate new Ocean Best Practices.
Impacts of stony coral tissue loss disease on the persistence of Caribbean cleaner gobies
Authors: Budd Kayla A. , Sikkel Paul C. , Brandt Marilyn E. , Costa Sophia V. , Smith Tyler B. , Nemeth Richard S.
Published: April 2024

Because they serve as the main architects of coral reefs, the distribution and abundance of stony coral species have major impacts on other associated community members. Thus, coral diseases can have significant cascading effects throughout the ecosystem. Stony coral tissue loss disease (SCTLD) is the most recent of many diseases documented to impact Caribbean stony corals. SCTLD is known to impact over 20 species of reef-building corals and can cause complete colony mortality of large corals in only one month. Among the coral species impacted are those occupied as cleaning stations by Caribbean cleaner gobies. This study examined the persistence of these gobies on living coral cleaning stations where SCTLD was most recently or not yet affected (emergent), recently established (epidemic), and well-established (endemic),. Timed surveys were conducted at nine reefs in the U.S. Virgin Islands between October 2019 and March 2021. Study sites were surveyed both before and after the outbreak/establishment of SCTLD where possible. Monitoring sites were established at six reefs by tagging 25 live coral cleaning stations at each of two endemic and two epidemic sites and 50 cleaning stations at each of two emergent sites. Goby abundance at each site was monitored at least five times from March 2020 to April 2021. Timed surveys found cleaner goby abundance was 50% lower in the endemic zone compared to epidemic and emergent zones. Overall, goby abundance declined on tagged cleaning stations throughout the course of this study at all sites. However, overall goby density within monitored areas remained stable across most sites from the beginning to the end of the study. One emergent site experienced a two-fold increase in goby density and one epidemic site experienced a decline in goby density. This suggests that gobies are remaining at the site but may be abandoning live coral cleaning stations as the individual colonies are affected by SCTLD. Given the benefit cleaner gobies have on local coral reef fishes, changes in cleaning activity associated with coral disease have the potential to negatively impact Caribbean reef fish communities.
The development and validation of automated machine learning models for predicting lymph node metastasis in Siewert type II T1 adenocarcinoma of the esophagogastric junction
Authors: Lu Chenghao , Liu Lu , Yin Minyue , Lin Jiaxi , Zhu Shiqi , Gao Jingwen , Qu Shuting , Xu Guoting , Liu Lihe , Zhu Jinzhou , Xu Chunfang
Published: April 2024

Background

Lymph node metastasis (LNM) is considered an essential prognosis factor for adenocarcinoma of the esophagogastric junction (AEG), which also affects the treatment strategies of AEG. We aimed to evaluate automated machine learning (AutoML) algorithms for predicting LNM in Siewert type II T1 AEG.

Methods

A total of 878 patients with Siewert type II T1 AEG were selected from the Surveillance, Epidemiology, and End Results (SEER) database to develop the LNM predictive models. The patients from two hospitals in Suzhou were collected as the test set. We applied five machine learning algorithms to develop the LNM prediction models. The performance of predictive models was assessed using various metrics including accuracy, sensitivity, specificity, the area under the curve (AUC), and receiver operating characteristic (ROC) curve.

Results

Patients with LNM exhibited a higher proportion of male individuals, a poor degree of differentiation, and submucosal infiltration, with statistical differences. The deep learning (DL) model demonstrated relatively good accuracy (0.713) and sensitivity (0.868) among the five models. Moreover, the DL model achieved the highest AUC (0.781) and sensitivity (1.000) in the test set.

Conclusion

The DL model showed good predictive performance among five AutoML models, indicating the advantage of AutoML in modeling LNM prediction in patients with Siewert type II T1 AEG.
Prevention and treatment strategies for kidney transplant recipients in the context of long-term existence of COVID-19
Authors: Zheng Zeyuan , Sun Huimin , Hu Xiaoyan , Xuan Zuodong , Fu Meiling , Bai Yang , Du Yifan , Liu Bin , Sui Xiuyuan , Zheng Jianzhong , Shao Chen
Published: April 2024

The sudden outbreak of coronavirus disease 2019 (COVID-19) in early 2020 posed a massive threat to human life and caused an economic upheaval worldwide. Kidney transplant recipients (KTRs) became susceptible to infection during the COVID-19 pandemic owing to their use of immunosuppressants, resulting in increased hospitalization and mortality rates. Although the current epidemic situation is alleviated, the long-term existence of COVID-19 still seriously threatens the life and health of KTRs with low immunity. The Omicron variant, a highly infectious but less-pathogenic strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has raised concerns among transplant physicians regarding managing KTRs diagnosed with this variant. However, currently, there are no clear and unified guidelines for caring for KTRs infected with this variant. Therefore, we aimed to summarize the ongoing research on drugs that can treat Omicron variant infections in KTRs and explore the potential of adjusting immunotherapy strategies to enhance their responsiveness to vaccines. Herein, we discuss the situation of KTRs since the emergence of COVID-19 and focus on various prevention and treatment strategies for KTRs since the Omicron variant outbreak. We hope to assist physicians in managing KTRs in the presence of long-term COVID-19 variants.
The role of volatile organic compounds for assessing characteristics and severity of non-cystic fibrosis bronchiectasis: an observational study
Authors: Gu Shu-Yi , Lu Hai-Wen , Bai Jiu-Wu , Yang Jia-Wei , Mao Bei , Yu Li , Xu Jin-Fu
Published: April 2024

Background

Hypoxic conditions and Pseudomonas aeruginosa (P. aeruginosa) infection are significant factors influencing the prognosis and treatment of patients with bronchiectasis. This study aimed to explore the potential for breath analysis to detect hypoxic conditions and P. aeruginosa infection in bronchiectasis patients by analyzing of volatile organic compounds (VOCs) in exhaled breath condensate (EBC).

Methods

EBC samples were collected from stable bronchiectasis patients and analyzed using solid phase microextraction-gas chromatography-mass spectrometry (SPME-GCMS). The association of VOCs with bronchiectasis patients' phenotypes including hypoxic conditions and P. aeruginosa isolation was analyzed, which may relate to the severity of bronchiectasis disease.

Results

Levels of 10-heptadecenoic acid, heptadecanoic acid, longifolene, and decanol in the hypoxia group were higher compared to the normoxia group. Additionally, the levels of 13-octadecenoic acid, octadecenoic acid, phenol, pentadecanoic acid, and myristic acid were increased in P. aeruginosa (+) group compared to the P. aeruginosa (–) group. Subgroup analysis based on the bronchiectasis severity index (BSI)reveled that the levels of 10-heptadecenoic acid, heptadecanoic acid, decanol, 13-octadecenoic acid, myristic acid, and pentadecanoic acid were higher in the severe group compared to the moderate group. Multivariate linear regression showed that 10-heptadecenoic acid and age were independent prognostic factors for bronchiectasis patients with hypoxia. Furthermore, octadecenoic acid, phenol and gender were identified as independent prognostic factors for bronchiectasis patients with P. aeruginosa isolation.

Conclusion

The study provides evidence that specific VOCs in EBC are correlated with the severity of bronchiectasis, and 10-heptadecenoic acid is shown to be a predictive marker for hypoxia condition in bronchiectasis patients.
Associations between genomic aberrations, increased nuchal translucency, and pregnancy outcomes: a comprehensive analysis of 2,272 singleton pregnancies in women under 35
Authors: Huang Jia , Wu Dong , He Jia-Huan , Wang Jing-Yuan , Li Xi , Wang Zheng-Yuan , Wang Yue , Liu Hong-Yan
Published: April 2024

Objectives

Regarding increased nuchal translucency (NT), the cutoff values used are heterogeneous in clinical practice, this study aims to assess the efficacy of prenatal detection for chromosomal abnormalities and pregnancy outcomes in fetuses with varying NT thicknesses, in order to provide data that supports informed prenatal diagnosis and genetic counseling for such cases.

Methods

We included 2,272 pregnant women under 35 with singleton pregnancies who underwent invasive prenatal diagnosis between 2014 and 2022. The cohort comprised 2,010 fetuses with increased NT (≥2.5 mm) and 262 fetuses with normal NT but exhibiting a single soft marker. Prenatal diagnoses were supported by chromosomal microarray (CMA) and copy number variation sequencing (CNV-seq) analyses.

Results

The detection rates of numerical chromosomal abnormalities were 15.4% (309/2,010) and 17.3% (297/1,717) in the NT ≥2.5 and ≥ 3.0 groups, respectively. Pathogenic/likely pathogenic CNV incidence increased with NT thickness (χ2 = 8.60, p < 0.05), peaking at 8.7% (22/254) in the NT 4.5–5.4 mm group. Structural defects were found in 18.4% of fetuses with NT values between 2.5 mm and 2.9 mm. Chromosomal abnormality rates in the isolated increased NT groups of 2.5–2.9 mm and 3.0–3.4 mm were 6.7% (16/239) and 10.0% (47/470), respectively, with no statistical significance (χ2 = 2.14, p > 0.05). Fetuses with NT thickness between 2.5 and 2.9 mm combined with the presence of soft markers or non-lethal structural abnormalities exhibited a significantly higher chromosomal abnormality risk (19.0%) compared to fetuses with isolated increased NT ranging from 3.5 to 4.4 mm (13.0%). Pregnancy termination rates increased with NT thickness (χ2 = 435.18, p < 0.0001), ranging from 12.0% (30/249) in the NT 2.5–2.9 mm group to 87.0% (141/162) in the NT ≥ 6.5 mm group.

Conclusion

CMA or CNV-seq exhibited good performance in identifying genomic aberrations in pregnancies with increased NT thickness. NT ranging from 2.5 mm to 2.9 mm elevated the risk of fetal chromosomal abnormalities, particularly when combined with other soft markers.
Live attenuated-nonpathogenic Leishmania and DNA structures as promising vaccine platforms against leishmaniasis: innovations can make waves
Authors: Seyed Negar , Taheri Tahereh , Rafati Sima
Published: April 2024

Leishmaniasis is a vector-borne disease caused by the protozoan parasite of Leishmania genus and is a complex disease affecting mostly tropical regions of the world. Unfortunately, despite the extensive effort made, there is no vaccine available for human use. Undoubtedly, a comprehensive understanding of the host-vector-parasite interaction is substantial for developing an effective prophylactic vaccine. Recently the role of sandfly saliva on disease progression has been uncovered which can make a substantial contribution in vaccine design. In this review we try to focus on the strategies that most probably meet the prerequisites of vaccine development (based on the current understandings) including live attenuated/non-pathogenic and subunit DNA vaccines. Innovative approaches such as reverse genetics, CRISP/R-Cas9 and antibiotic-free selection are now available to promisingly compensate for intrinsic drawbacks associated with these platforms. Our main goal is to call more attention toward the prerequisites of effective vaccine development while controlling the disease outspread is a substantial need.
Causal relationship between gut microbiota and chronic renal failure: a two-sample Mendelian randomization study
Authors: Liu Xingzheng , Mo Jinying , Yang Xuerui , Peng Ling , Zeng Youjia , Zheng Yihou , Song Gaofeng
Published: April 2024

Background

Observational studies and some experimental investigations have indicated that gut microbiota are closely associated with the incidence and progression of chronic renal failure. However, the causal relationship between gut microbiota and chronic renal failure remains unclear. The present study employs a two-sample Mendelian randomization approach to infer the causal relationship between gut microbiota and chronic renal failure at the genetic level. This research aims to determine whether there is a causal effect of gut microbiota on the risk of chronic renal failure, aiming to provide new evidence to support targeted gut therapy for the treatment of chronic renal failure.

Methods

Employing genome-wide association study (GWAS) data from the public MiBioGen and IEU OpenGWAS platform, a two-sample Mendelian randomization analysis was conducted. The causal relationship between gut microbiota and chronic renal failure was inferred using five different methods: Inverse Variance Weighted, MR-Egger, Weighted Median, Simple Mode, and Weighted Mode. The study incorporated sensitivity analyses that encompassed evaluations for pleiotropy and heterogeneity. Subsequently, the results of the Mendelian randomization analysis underwent a stringent correction for multiple testing, employing the False Discovery Rate method to enhance the validity of our findings.

Results

According to the results from the Inverse Variance Weighted method, seven bacterial genera show a significant association with the outcome variable chronic renal failure. Of these, Ruminococcus (gauvreauii group) (OR = 0.82, 95% CI = 0.71–0.94, p = 0.004) may act as a protective factor against chronic renal failure, while the genera Escherichia-Shigella (OR = 1.22, 95% CI = 1.08–1.38, p = 0.001), Lactococcus (OR = 1.1, 95% CI = 1.02–1.19, p = 0.013), Odoribacter (OR = 1.23, 95% CI = 1.03–1.49, p = 0.026), Enterorhabdus (OR = 1.14, 95% CI = 1.00–1.29, p = 0.047), Eubacterium (eligens group) (OR = 1.18, 95% CI = 1.02–1.37, p = 0.024), and Howardella (OR = 1.18, 95% CI = 1.09–1.28, p < 0.001) may be risk factors for chronic renal failure. However, after correction for multiple comparisons using False Discovery Rate, only the associations with Escherichia-Shigella and Howardella remain significant, indicating that the other genera have suggestive associations. Sensitivity analyses did not reveal any pleiotropy or heterogeneity.

Conclusion

Our two-sample Mendelian randomization study suggests that the genera Escherichia-Shigella and Howardella are risk factors for chronic renal failure, and they may serve as potential targets for future therapeutic interventions. However, the exact mechanisms of action are not yet clear, necessitating further research to elucidate their precise roles fully.
Dysexecutive difficulty and subtle everyday functional disabilities: the digital Trail Making Test
Authors: Libon David J. , Swenson Rod , Tobyne Sean , Jannati Ali , Schulman Daniel , Price Catherine C. , Lamar Melissa , Pascual-Leone Alvaro
Published: April 2024

Background

Digital neuropsychological tests reliably capture real-time, process-based behavior that traditional paper/pencil tests cannot detect, enabling earlier detection of neurodegenerative illness. We assessed relations between informant-based subtle and mild functional decline and process-based features extracted from the digital Trail Making Test-Part B (dTMT-B).

Methods

A total of 321 community-dwelling participants (56.0% female) were assessed with the Functional Activities Questionnaire (FAQ) and the dTMT-B. Three FAQ groups were constructed: FAQ = 0 (unimpaired); FAQ = 1–4 (subtle impairment); FAQ = 5–8 (mild impairment).

Results

Compared to the FAQ-unimpaired group, other groups required longer pauses inside target circles (p < 0.050) and produced more total pen strokes to complete the test (p < 0.016). FAQ-subtle participants required more time to complete the entire test (p < 0.002) and drew individual lines connecting successive target circles slower (p < 0.001) than FAQ-unimpaired participants. Lines connecting successive circle targets were less straight among FAQ-mild, compared to FAQ-unimpaired participants (p < 0.044). Using stepwise nominal regression (reference group = FAQ-unimpaired), pauses inside target circles classified other participants into their respective groups (p < 0.015, respectively). Factor analysis using six dTMT-B variables (oblique rotation) yielded a two-factor solution related to impaired motor/cognitive operations (48.96% variance explained) and faster more efficient motor/cognitive operations (28.88% variance explained).

Conclusion

Digital assessment technology elegantly quantifies occult, nuanced behavior not previously appreciated, operationally defines critical underlying neurocognitive constructs related to functional abilities, and yields selected process-based scores that outperform traditional paper/pencil test scores for participant classification. When brought to scale, the dTMT-B test could be a sensitive tool to detect subtle-to-mild functional deficits in emergent neurodegenerative illnesses.
Case report: Rapid-onset parkinsonism after a hornet sting
Authors: Tomic Svetlana , Zjalic Milorad , Popovic Zvonimir , Krivdic Dupan Zdravka , Heffer Marija , Snajder Mujkic Darija , Mandic Dario , Guljas Silva , Petrovic Igor N.
Published: April 2024

Neurological manifestations with basal ganglia involvement following Hymenoptera stings are rare and clinically ill-defined conditions. We present a patient with acute parkinsonism non-responsive to levodopa, who developed striatal lesions after a hornet sting. We report his response to immunomodulatory treatment and subsequent clinical and brain magnetic resonance imaging (MRI) follow-up. We also searched the literature for patients with acute extrapyramidal syndromes following an insect sting. Fourteen cases have been published; 12 of them are reviewed here. The majority of cases presented with symmetric akinetic syndrome with axial rigidity and/or gait impairment. Six patients were treated with levodopa and only two of these had a modest response to therapy. Brain MRI/computed tomography scan revealed lesions of the basal ganglia, which resulted in fatal outcome in four patients, whereas only one achieved complete recovery. Clinicians should be aware of this rare but devastating cause of acute-onset parkinsonism and specific clinical presentation of this condition, and should consider prompt and prolonged immunomodulatory treatment to prevent irreversible basal ganglia damage.
Development and evaluation of a BCI-neurofeedback system with real-time EEG detection and electrical stimulation assistance during motor attempt for neurorehabilitation of children with cerebral palsy
Authors: Behboodi Ahad , Kline Julia , Gravunder Andrew , Phillips Connor , Parker Sheridan M. , Damiano Diane L.
Published: April 2024

In the realm of motor rehabilitation, Brain-Computer Interface Neurofeedback Training (BCI-NFT) emerges as a promising strategy. This aims to utilize an individual’s brain activity to stimulate or assist movement, thereby strengthening sensorimotor pathways and promoting motor recovery. Employing various methodologies, BCI-NFT has been shown to be effective for enhancing motor function primarily of the upper limb in stroke, with very few studies reported in cerebral palsy (CP). Our main objective was to develop an electroencephalography (EEG)-based BCI-NFT system, employing an associative learning paradigm, to improve selective control of ankle dorsiflexion in CP and potentially other neurological populations. First, in a cohort of eight healthy volunteers, we successfully implemented a BCI-NFT system based on detection of slow movement-related cortical potentials (MRCP) from EEG generated by attempted dorsiflexion to simultaneously activate Neuromuscular Electrical Stimulation which assisted movement and served to enhance sensory feedback to the sensorimotor cortex. Participants also viewed a computer display that provided real-time visual feedback of ankle range of motion with an individualized target region displayed to encourage maximal effort. After evaluating several potential strategies, we employed a Long short-term memory (LSTM) neural network, a deep learning algorithm, to detect the motor intent prior to movement onset. We then evaluated the system in a 10-session ankle dorsiflexion training protocol on a child with CP. By employing transfer learning across sessions, we could significantly reduce the number of calibration trials from 50 to 20 without compromising detection accuracy, which was 80.8% on average. The participant was able to complete the required calibration trials and the 100 training trials per session for all 10 sessions and post-training demonstrated increased ankle dorsiflexion velocity, walking speed and step length. Based on exceptional system performance, feasibility and preliminary effectiveness in a child with CP, we are now pursuing a clinical trial in a larger cohort of children with CP.
Comparative efficacy and safety of targeted therapy and immunotherapy for HER2-positive breast cancer: a systematic review and network meta-analyses
Authors: Gu Suyu , Liu Yuting , Huang Yufan , Lin Wenzheng , Li Ke
Published: April 2024

Background

In recent years, novel therapies targeting specific molecular pathways and immunotherapies have exhibited promising outcomes for treating human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Our work aimed to assess the effectiveness and safety of these emerging treatment regimens for this disease.

Material and methods

We systematically searched databases including PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials their inception to August 2023 to identify relevant randomized controlled trials (RCTs). The quality of eligible RCTs was evaluated with the Cochrane risk-of-bias tool, version 2 (RoB2). Investigated outcomes encompassed progression-free survival (PFS), overall survival (OS), disease-free survival (DFS), pathologic complete remission (pCR), and adverse events (AEs). They were expressed as hazard ratio (HR) with 95% conference intervals (CI) or risk ratio (RR) with 95% CI.

Results

Our analysis identified a total of 28 RCTs suitable for inclusion in the NMA. Regarding the PFS, all these treatment regimens exhibited comparable effectiveness. In terms of OS, Capecitabine+Trastuzumab, Lapatinib+Trastuzumab and Pyrotinib+Capecitabine exhibited better effect compared to other treatments. Regarding pCR and AEs, all these treatment regimens exhibited comparable effectiveness, especially Lapatinib+Trastuzumab and Pyrotinib+Capecitabine.

Conclusion

Our study highlights the prominent role of targeted therapies and immunotherapies in treating HER2-positive breast cancer. The efficacy of trastuzumab-containing regimens was superior to other treatment options, while maintaining a comparable safety profile. Based on these findings, trastuzumab-containing regimens emerge as a preferable and recommended choice in clinical practice for managing HER2-positive breast cancer.

Systematic Review Registration

PROSPERO, identifier CRD42023414348.
Radical nephrectomy for a giant chromophobe renal cell carcinoma diagnosed > 17 years previously: a case report and literature review
Authors: Lan Jianhua , Lan Dong , Yuan Wenqiang , Ying Qiao , He Jiahong , Gu Yonglin
Published: April 2024

Early diagnosis of renal cell carcinoma relies on imaging tests such as ultrasound, computed tomography, or magnetic resonance imaging. Since surgery is associated with a favorable prognosis, the standard treatment for clinically limited renal cell carcinoma remains surgical resection. Among asymptomatic patients with localized renal cell carcinoma, a small number refuse surgical treatment and survive. We report a case involving a 59-year-old female who underwent a difficult radical nephrectomy 17 years after being diagnosed with malignant tumors due to primary renal cell carcinoma.
Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy and intraoperative radiation therapy in the management of gallbladder cancer: a case report
Authors: Alaswad Marwan , Otry Abdullah Al , Alhosainy Ziad , Elkordy Fadwa , Sabbah Belal Nedal , Arabi Tarek Ziad , Abdulkader Humzah , Ghanayem Obaida Fadi , Azzam Ayman Zaki , Amin Tarek
Published: April 2024

Gallbladder cancer (GBC) is a rare and highly aggressive malignancy, often characterized by nonspecific clinical presentations and late diagnosis, which contribute to its poor prognosis. It is commonly detected at advanced stages, leading to low survival rates. Surgical resection is the primary treatment, with the extent of surgery depending on the T stage of the cancer. In advanced cases, surgery is only considered if it can potentially be curative. Despite various treatment approaches for advanced GBC, survival outcomes remain poor. In our case series, we introduce a novel treatment approach combining cytoreductive surgery, intraoperative radiation therapy, and hyperthermic intraperitoneal chemotherapy. Remarkably, we observed a 100% one-year survival rate, with one patient achieving eight years of disease-free survival without recurrence or metastasis. This aggressive treatment strategy did not lead to increased morbidity or mortality, suggesting its safety and feasibility. However, larger-scale studies are required to draw definitive conclusions.
Clinical outcomes of intermittent panitumumab based-therapy for previously treated older patient with metastatic colorectal cancer: a case report and review of literature
Authors: Rosati Gerardo , Annunziata Luigi , Scarano Enrico , Dapoto Francesca , Bilancia Domenico
Published: April 2024

Background

Metastatic colorectal cancer is one of the most common causes of cancer death worldwide, and its incidence increases with age. Treating an older RAS and BRAF wild-type patient represents a challenge for the medical oncologist, even more so for those patients defined as “vulnerable” and undergoing at least two lines of therapy. In this context, recent evidence supports the role of retreatment with anti-EGFR inhibitors and the use of liquid biopsy. However, frequent skin toxicity constitutes a limitation of therapy, especially in older people. Since it has been described that continuous administration of these monoclonal antibodies leads to acquired resistance to anti-EGFRs, with consequent therapeutic failure, an intermittent strategy with chemotherapy plus an anti-EGFR could help maintain the efficacy of the treatment over time, delaying the resistance and improving patients’ quality of life.

Case presentation

In this case report, we describe the case of an older RAS and BRAF wild-type patient reporting a clinical response after first-line chemotherapy with FOLFOX + panitumumab, subsequently interrupted in the absence of disease progression. After radiological worsening and two additional lines of therapy, the reintroduction of panitumumab plus 5-fluorouracil, administered with a stop-and-go strategy, allowed the patient to benefit from the same drugs for 2 years from diagnosis, to achieve a clinical response during fourth-line treatment lasting more than 3 years, to delay resistance and to avoid unacceptable anti-EGFR skin toxicity. This patient, who died from a myocardial infarction more than 5 years after diagnosis, represents the case of a good synergy between molecular profile of disease and reintroduction of an anti-EGFR with intermittent strategy.
Personality systems interactions theory: an integrative framework complementing the study of the motivational and volitional dynamics underlying adjustment to chronic pain
Authors: Kästner Anne , Petzke Frank
Published: April 2024

In the endeavor to advance our understanding of interindividual differences in dealing with chronic pain, numerous motivational theories have been invoked in the past decade. As they focus on relevant, yet different aspects of the dynamic, multilevel processes involved in human voluntary action control, research findings seem fragmented and inconsistent. Here we present Personality Systems Interactions theory as an integrative meta-framework elucidating how different motivational and volitional processes work in concert under varying contextual conditions. PSI theory explains experience and behavior by the relative activation of four cognitive systems that take over different psychological functions during goal pursuit. In this way, it may complement existing content-related explanations of clinical phenomena by introducing a functional, third-person perspective on flexible goal management, pain acceptance and goal maintenance despite pain. In line with emerging evidence on the central role of emotion regulation in chronic pain, PSI theory delineates how the self-regulation of positive and negative affect impacts whether behavior is determined by rigid stimulus-response associations (i.e., habits) or by more abstract motives and values which afford more behavioral flexibility. Along with testable hypotheses, multimodal interventions expected to address intuitive emotion regulation as a central process mediating successful adaptation to chronic pain are discussed.
Hypoxic preacclimatization combining intermittent hypoxia exposure with physical exercise significantly promotes the tolerance to acute hypoxia
Authors: Xie Jiaxin , Xie Shenwei , Zhong Zhifeng , Dong Huaping , Huang Pei , Zhou Simin , Tian Huaijun , Zhang Jijian , Wu Yu , Li Peng
Published: April 2024

Background: Both hypoxia exposure and physical exercise before ascending have been proved to promote high altitude acclimatization, whether the combination of these two methods can bring about a better effect remains uncertain. Therefore, we designed this study to evaluate the effect of hypoxic preacclimatization combining intermittent hypoxia exposure (IHE) and physical exercise on the tolerance to acute hypoxia and screen the optimal preacclimatization scheme among the lowlanders.

Methods: A total of 120 Han Chinese young men were enrolled and randomly assigned into four groups, including the control group and three experimental groups with hypoxic preacclimatization of 5-day rest, 5-day exercise, and 3-day exercise in a hypobaric chamber, respectively. Main physical parameters for hypoxia acclimatization, AMS incidence, physical and mental capacity were measured for each participant in the hypobaric chamber simulated to the altitude of 4500 m in the effect evaluation stage. The effect was compared between different schemes.

Results: During the effect evaluation stage, SpO2 of the 5-day rest group and 5-day exercise group was significantly higher than that of the control group (p = 0.001 and p = 0.006, respectively). The participants with 5-day rest had significantly lower HR than the controls (p = 0.018). No significant differences of AMS incidence were found among the four groups, while the proportion of AMS headache symptom (moderate and severe vs. mild) was significantly lower in the 3-day exercise group than that in the control group (p = 0.002). The 5-day exercise group had significantly higher VO2max, than the other three groups (p = 0.033, p < 0.001, and p = 0.023, respectively). The 5-day exercise group also had significantly higher digital symbol and pursuit aiming test scores, while shorter color selection reaction time than the control group (p = 0.005, p = 0.005, and p = 0.004, respectively).

Conclusion: Hypoxic preacclimatization combining IHE with physical exercise appears to be efficient in promoting the tolerance to acute hypoxia. Hypoxia duration and physical exercise of moderate intensity are helpful for improvement of SpO2 and HR, relief of AMS headache symptoms, and enhancement of mental and physical operation capacity.
Thidiazuron combined with cyclanilide modulates hormone pathways and ROS systems in cotton, increasing defoliation at low temperatures
Authors: Shu Hongmei , Sun Shangwen , Wang Xiaojing , Chen Jian , Yang Changqin , Zhang Guowei , Han Huanyong , Li Zhikang , Liang Ting , Liu Ruixian
Published: April 2024

Low temperatures decrease the thidiazuron (TDZ) defoliation efficiency in cotton, while cyclanilide (CYC) combined with TDZ can improve the defoliation efficiency at low temperatures, but the mechanism is unknown. This study analyzed the effect of exogenous TDZ and CYC application on cotton leaf abscissions at low temperatures (daily mean temperature: 15°C) using physiology and transcriptomic analysis. The results showed that compared with the TDZ treatment, TDZ combined with CYC accelerated cotton leaf abscission and increased the defoliation rate at low temperatures. The differentially expressed genes (DEGs) in cotton abscission zones (AZs) were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to compare the enriched GO terms and KEGG pathways between the TDZ treatment and TDZ combined with CYC treatment. TDZ combined with CYC could induce more DEGs in cotton leaf AZs at low temperatures, and these DEGs were related to plant hormone and reactive oxygen species (ROS) pathways. CYC is an auxin transport inhibitor. TDZ combined with CYC not only downregulated more auxin response related genes but also upregulated more ethylene and jasmonic acid (JA) response related genes at low temperatures, and it decreased the indole-3-acetic acid (IAA) content and increased the JA and 1-aminocyclopropane-1-carboxylic acid (ACC) contents, which enhanced cotton defoliation. In addition, compared with the TDZ treatment alone, TDZ combined with CYC upregulated the expression of respiratory burst oxidase homologs (RBOH) genes and the hydrogen peroxide content in cotton AZs at low temperatures, which accelerated cotton defoliation. These results indicated that CYC enhanced the TDZ defoliation efficiency in cotton by adjusting hormone synthesis and response related pathways (including auxin, ethylene, and JA) and ROS production at low temperatures.
Screening candidate genes for fruit size based on QTL-seq in Chinese jujube
Authors: Pan Yiling , Luo Yujia , Bao Jingkai , Wu Cuiyun , Wang Jiurui , Liu Mengjun , Yan Fenfen
Published: April 2024

Introduction

Fruit size is an important economic trait affecting jujube fruit quality, which has always been the focus of marker-assisted breeding of jujube traits. However, despite a large number of studies have been carried out, the mechanism and key genes regulating jujube fruit size are mostly unknown.

Methods

In this study, we used a new analysis method Quantitative Trait Loci sequencing (QTL-seq) (bulked segregant analysis) to screen the parents ‘Yuhong’ and ‘Jiaocheng 5’ with significant phenotypic differences and mixed offspring group with extreme traits of large fruit and small fruit, respectively, and, then, DNA mixed pool sequencing was carried out to further shortening the QTL candidate interval for fruit size trait and excavated candidate genes for controlling fruit size.

Results

The candidate intervals related to jujube fruit size were mainly located on chromosomes 1, 5, and 10, and the frequency of chromosome 1 was the highest. Based on the QTL-seq results, the annotation results of ANNOVAR were extracted from 424 SNPs (single-nucleotide polymorphisms) and 164 InDels (insertion-deletion), from which 40 candidate genes were selected, and 37 annotated candidate genes were found in the jujube genome. Four genes (LOC107428904, LOC107415626, LOC125420708, and LOC107418290) that are associated with fruit size growth and development were identified by functional annotation of the genes in NCBI (National Center for Biotechnology Information). The genes can provide a basis for further exploration and identification on genes regulating jujube fruit size.

Discussion

In summary, the data obtained in this study revealed that QTL intervals and candidate genes for fruit size at the genomic level provide valuable resources for future functional studies and jujube breeding.