bluuebunny/crossref_metadata_2025 huggingface dataset:
“Through the Valley of the Shadow of Death”
Authors: David Anthony
Published: September 2024

This essay chronicles my personal journey of uncovering a truth that contradicted my long-held assumptions, resulting in a profound professional reckoning. It began with my discovery of a treasure trove of 350 glass plate negatives, masterpieces captured between 1920 and 1940, which led me to write a biography of the photographer, Benedict Stolz, a German Benedictine monk. A central figure in this biography was Hermann Keller, Stolz’s childhood friend and, in his day, a renowned theologian, philosopher, and Hebraist. I portrayed Keller as a Nazi war criminal and associate of SS leader Reinhard Heydrich, based on numerous secondary sources. However, shortly before publication, an interview with a nun who had known Keller challenged this narrative, attributing the “erroneous charges” against him to the mistakes of one historian that were subsequently echoed by others. After years of doubting her claims, I was confronted with evidence proving Keller’s innocence, prompting a critical reflection on how historians, including myself, can unwittingly propagate inaccuracies.
The Past in the Present: Eleanor Antin, Jewish Art and 1990s America
Authors: Julius Chloë
Published: September 2024

This essay situates two works by Eleanor Antin—the film The Man Without a World (1991), and the installation Vilna Nights (1993)—in the context of Jewish art as it was articulated in 1990s America. During this period, efforts were made by scholars, curators—and some artists—towards a new Jewish art that would be consummate with other contemporaneous identity-based practices. Although these efforts did not birth a new Jewish art, they did instigate a revived interest in the history of Eastern European Jewry. This was Antin’s subject in both The Man Without a World and Vilna Nights, but the representation of this history in both works challenged the nostalgia that it courted in other corners of 1990s Jewish art.
Intracerebral delivery of antiseizure medications by microinvasive neural implants
Authors: Jackson Hannah D , Cotler Max J , Saunders Gerald W , Cornelssen Carena A , West Peter J , Metcalf Cameron S , Wilcox Karen S , Cima Michael J
Published: September 2024

Focal epilepsy is a difficult disease to treat as two-thirds of patients will not respond to oral anti-seizure medications (ASMs) or have severe off-target effects that lead to drug discontinuation. Current non-pharmaceutical treatment methods (resection or ablation) are underutilized due to the associated morbidities, invasive nature and inaccessibility of seizure foci. Less invasive non-ablative modalities may potentially offer an alternative. Targeting the seizure focus in this way may avoid unassociated critical brain structures to preserve function and alleviate seizure burden.

Here we report use of an implantable, miniaturized neural drug delivery system [microinvasive neural implant infusion platform (MINI)] to administer ASMs directly to the seizure focus in a mouse model of temporal lobe epilepsy. We examined the effect local delivery of phenobarbital and valproate had on focal seizures, as well as adverse effects, and compared this to systemic delivery.

We show that local delivery of phenobarbital and valproate using our chronic implants significantly reduced focal seizures at all doses given. Furthermore, we show that local delivery of these compounds resulted in no adverse effects to motor function, whereas systemic delivery resulted in significant motor impairment.

The results of this study demonstrate the potential of ASM micro dosing to the epileptic focus as a treatment option for people with drug resistant epilepsy. This technology could also be applied to a variety of disease states, enabling a deeper understanding of focal drug delivery in the treatment of neurological disorders.
Longitudinal analysis of glymphatic function in amyotrophic lateral sclerosis and primary lateral sclerosis
Authors: Sharkey Rachel J , Cortese Filomeno , Goodyear Bradley G , Korngut Lawrence W , Jacob Sarah M , Sharkey Keith A , Kalra Sanjay , Nguyen Minh Dang , Frayne Richard , Pfeffer Gerald
Published: September 2024

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of motor neurons in the brain and spinal cord. Accumulation of misfolded proteins is central to the pathogenesis of ALS and the glymphatic system is emerging as a potential therapeutic target to reduce proteinopathy. Using diffusion tensor imaging analysis along the perivascular spaces (DTI-ALPS) to assess glymphatic function, we performed a longitudinal analysis of glymphatic function in ALS and compared it to a disorder in the motor neuron disease spectrum, primary lateral sclerosis (PLS).

From a cohort of 45 participants from the Calgary site in the CALSNIC study (Canadian ALS Neuroimaging Consortium), including 18 ALS, 5 PLS and 22 control participants, DTI-ALPS was analysed and correlated to clinical features (age, sex, disease presentation, disease severity and progression rate) and white matter hyperintensity burden. This included longitudinal measurements at three time points, 4 months apart.

The DTI-ALPS index was reduced in ALS participants compared with PLS and control participants across all three time points. There was no association with clinical factors; however, the index tended to decline with advancing age. Our study suggests heterogeneity in glymphatic dysfunction in motor neuron diseases that may be related to the underlying pathogenesis.
Linear Statistics of Determinantal Point Processes and Norm Representations
Authors: Levi Matteo , Marzo Jordi , Ortega-Cerdà Joaquim
Published: September 2024

We study the asymptotic behavior of the fluctuations of smooth and rough linear statistics for determinantal point processes on the sphere and on the Euclidean space. The main tool is the generalization of some norm representation results for functions in Sobolev spaces and in the space of functions of bounded variation.
Lascoux Polynomials and Subdivisions of Gelfand–Zetlin Polytopes
Authors: Presnova Ekaterina , Smirnov Evgeny
Published: September 2024

We give a new combinatorial description for Grassmannian Grothendieck polynomials in terms of subdivisions of Gelfand–Zetlin polytopes. Moreover, these subdivisions also provide a description of Lascoux polynomials. This generalizes a similar result on key polynomials by Kiritchenko, Smirnov, and Timorin.
Luminal progenitor and mature cells are more susceptible than basal cells to radiation-induced DNA double-strand breaks in rat mammary tissue
Authors: Nagata Kento , Nishimura Mayumi , Daino Kazuhiro , Nishimura Yukiko , Hattori Yuya , Watanabe Ritsuko , Iizuka Daisuke , Yokoya Akinari , Suzuki Keiji , Kakinuma Shizuko , Imaoka Tatsuhiko
Published: September 2024

Ionizing radiation promotes mammary carcinogenesis. Induction of DNA double-strand breaks (DSBs) is the initial event after radiation exposure, which can potentially lead to carcinogenesis, but the dynamics of DSB induction and repair are not well understood at the tissue level. In this study, we used female rats, which have been recognized as a useful experimental model for studying radiation effects on the mammary gland. We focused on differences in DSB kinetics among basal cells, luminal progenitor and mature cells in different parts of the mammary duct. 53BP1 foci were used as surrogate markers of DSBs, and 53BP1 foci in each mammary epithelial cell in immunostained tissue sections were counted 1–24 h after irradiation and fitted to an exponential function of time. Basal cells were identified as cytokeratin (CK) 14+ cells, luminal progenitor cells as CK8 + 18low cells and luminal mature cells as CK8 + 18high cells. The number of DSBs per nucleus tended to be higher in luminal cells than basal cells at 1 h post-irradiation. A model analysis indicated that basal cells in terminal end buds (TEBs), which constitute the leading edge of the mammary duct, had significantly fewer initial DSBs than the two types of luminal cells, and there was no significant difference in initial amount among the cell types in the subtending duct. The repair rate did not differ among mammary epithelial cell types or their locations. Thus, luminal progenitor and mature cells are more susceptible to radiation-induced DSBs than are basal cells in TEBs.
Drought-dependent regulation of cell coupling in Arabidopsis leaf epidermis requires plasmodesmal protein NHL12
Authors: Ayyoub Anam , Yu Xiuyuan , Zhang Xingjian , Gao Chen , Li Jiazhou , Yin Shijiao , Chen Shaolin , Liesche Johannes
Published: September 2024

The cytoplasm of most plant cells is connected by membrane-lined cell wall channels, the plasmodesmata (PD). Dynamic regulation of sugar, hormone, and protein diffusion through PD is essential for plant development and stress responses. Understanding this regulation requires knowledge of factors and mechanisms that control PD permeability through the modulation of callose levels in the cell wall around PD openings. We investigated PD regulation in leaf epidermal cells in relation to drought stress in Arabidopsis. PD-mediated cell wall permeability was decreased by drought stress and the hormone abscisic acid (ABA), and we tested how this related to several PD-associated genes with drought-responsive expression. Mutants of NON-RACE SPECIFIC DISEASE RESISTANCE/HIN1 HAIRPIN-INDUCED-LIKE 12 (NHL12) showed relatively low PD permeability that was unaffected by drought or ABA treatment. Overexpression of NHL12 in Nicotiana benthamiana epidermal cells increased PD permeability. Moreover, we showed that NHL12 can potentially interact with the callose synthase regulator NHL3 and we explored the effect of NHL12 abundance and/or lower interface permeability on ABA signaling genes. Our results indicate that NHL12 is a drought-responsive negative regulator of PD callose levels and, thereby, interface permeability. Results are discussed in relation to PD function during drought stress and the regulation of intercellular transport.
Logics for contact and measure
Authors: Balbiani Philippe , Gougeon Quentin , Tinchev Tinko
Published: September 2024

We enrich contact algebras with a new binary relation that compares the size of regions, and provide axiom systems for various logics of contact and measure. Our contribution is three-fold: (1) we characterize the relations on a Boolean algebra that derive from a measure, thereby improving an old result of Kraft, Pratt and Seidenberg; (2) for all $n \geq 1$, we axiomatize the logic of regular closed sets of ${\mathbb{R}}^{n}$ with null boundary; (3) considering a broad class of equational theories that contains all logics of contact, we prove that they all have unitary or finitary unification, and that unification and admissibility are decidable.
Baryon acoustic oscillation theory and modelling systematics for the DESI 2024 results
Authors: Chen S -F , Howlett C , White M , McDonald P , Ross A J , Seo H -J , Padmanabhan N , Aguilar J , Ahlen S , Alam S , Alves O , Andrade U , Blum R , Brooks D , Chen X , Cole S , Dawson K , de la Macorra A , Dey A , Ding Z , Doel P , Ferraro S , Font-Ribera A , Forero-Sánchez D , Forero-Romero J E , Garcia-Quintero C , Gaztañaga E , Gontcho S G A , Hanif M M S , Honscheid K , Kisner T , Kremin A , Lambert A , Landriau M , Levi M E , Manera M , Meisner A , Mena-Fernández J , Miquel R , Munoz-Gutierrez A , Paillas E , Palanque-Delabrouille N , Percival W J , Pérez-Fernández A , Prada F , Rashkovetskyi M , Rezaie M , Rosado-Marin A , Rossi G , Ruggeri R , Sanchez E , Schlegel D , Silber J , Tarlé G , Vargas-Magaña M , Weaver B A , Yu J , Yuan S , Zhou R , Zhou Z
Published: September 2024

This paper provides a comprehensive overview of how fitting of baryon acoustic oscillations (BAO) is carried out within the upcoming Dark Energy Spectroscopic Instrument’s (DESI) 2024 results using its DR1 data set, and the associated systematic error budget from theory and modelling of the BAO. We derive new results showing how non-linearities in the clustering of galaxies can cause potential biases in measurements of the isotropic ($\alpha _{\mathrm{iso}}$) and anisotropic ($\alpha _{\mathrm{ap}}$) BAO distance scales, and how these can be effectively removed with an appropriate choice of reconstruction algorithm. We then demonstrate how theory leads to a clear choice for how to model the BAO and develop, implement, and validate a new model for the remaining smooth-broad-band (i.e. without BAO) component of the galaxy clustering. Finally, we explore the impact of all remaining modelling choices on the BAO constraints from DESI using a suite of high-precision simulations, arriving at a set of best practices for DESI BAO fits, and an associated theory and modelling systematic error. Overall, our results demonstrate the remarkable robustness of the BAO to all our modelling choices and motivate a combined theory and modelling systematic error contribution to the post-reconstruction DESI BAO measurements of no more than 0.1 per cent (0.2 per cent) for its isotropic (anisotropic) distance measurements. We expect the theory and best practices laid out to here to be applicable to other BAO experiments in the era of DESI and beyond.
Class origin, intergenerational transfers, and the gender wealth gap
Authors: Trinh Nhat An
Published: September 2024

This study pursues two objectives: First, to describe how gender disparities in wealth levels vary by parental class and second, to examine the contribution of the gendered allocation of parental wealth to these differences. It thereby sheds light on the interplay between family background and gender in shaping wealth inequality. Using representative survey data from Germany, I find pronounced absolute and relative gaps in personal net wealth to the disadvantage of women. The largest wealth gaps are observed between men and women from the most advantaged backgrounds, for whom parental transfers of business and financial assets are strongly gendered. For these individuals, gender gaps would be reduced by around 40% if transfers were allocated equally. For those from lower class origins, equalizing transfers would not reduce gender gaps despite observed differences in the allocation of real estate and cash. Intergenerational transfers thus emerge as driver of gender wealth inequality at the very top of the class origin hierarchy.
A Critical Look at Racism in the Clinical Learning Environment
Authors: Poitevien Patricia , Sotto-Santiago Sylk
Published: September 2024

Academic medicine has long acknowledged the importance of diversity, equity, and inclusion (DEI) in the pursuit of health equity. Despite this recognition, the clinical learning environment (CLE) has struggled to foster an equitable and inclusive ecosystem that supports diverse learners and faculty.

Efforts to dismantle racism in medicine represent an important approach to supporting diverse learners and faculty in the CLE, but they have fallen short of their intended impact. The reasons for this failure are complex and may include a limited understanding of the impact of racism and a misguided conviction that knowledge of harm suffered by minoritized groups is a sufficient driver of change.

To advance understanding and increase motivation to dismantle racist systems within academic medicine, this paper posits 2 frameworks, Interest Convergence (IC) and Critical Whiteness Study (CWS). IC asserts that racial equity progresses only when it aligns with the interests of the majority, while CWS examines how Whiteness as a social construct upholds power and privilege, often to the detriment of White individuals themselves.

Utilizing these frameworks, the authors detail how Whiteness negatively impacts the health of White people and impedes entry to medical school for low- and middle-income, first-generation White students. The authors illustrate how practices—such as patient- and family-centered care and competency-based medical education—which are intended to improve care and medical education for all, are fully aligned with and integral to DEI principles. The authors conclude that racism and upholding Whiteness cause harm to majority as well as minoritized peoples, while DEI principles provide the foundation for best practices in the CLE and improve outcomes for all.
Chinese national clinical practice guideline on diagnosis and treatment of biliary tract cancers
Authors: Wang Xu’an , Bai Yongrui , Chai Ningli , Li Yexiong , Linghu Enqiang , Wang Liwei , Liu Yingbin ,   Society of Hepato-pancreato-biliary Surgery of Chinese Research Hospital Association, Society of Digestive Endoscopy of the Chinese Medical Association, Chinese Medical Journal Clinical Practice Guideline Collaborative
Published: September 2024

Background:

Biliary tract carcinoma (BTC) is relatively rare and comprises a spectrum of invasive tumors arising from the biliary tree. The prognosis is extremely poor. The incidence of BTC is relatively high in Asian countries, and a high number of cases are diagnosed annually in China owing to the large population. Therefore, it is necessary to clarify the epidemiology and high-risk factors for BTC in China. The signs associated with BTC are complex, often require collaborative treatment from surgeons, endoscopists, oncologists, and radiation therapists. Thus, it is necessary to develop a comprehensive Chinese guideline for BTC.

Methods:

This clinical practice guideline (CPG) was developed following the process recommended by the World Health Organization. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to assess the certainty of evidence and make recommendations. The full CPG report was reviewed by external guideline methodologists and clinicians with no direct involvement in the development of this CPG. Two guideline reporting checklists have been adhered to: Appraisal of Guidelines for Research and Evaluation (AGREE) and Reporting Items for practice Guidelines in Healthcare (RIGHT).

Results:

The guideline development group, which comprised 85 multidisciplinary clinical experts across China. After a controversies conference, 17 clinical questions concerning the prevention, diagnosis, and treatment of BTC were proposed. Additionally, detailed descriptions of the surgical principles, perioperative management, chemotherapy, immunotherapy, targeted therapy, radiotherapy, and endoscopic management were proposed.

Conclusions:

The guideline development group created a comprehensive Chinese guideline for the diagnosis and treatment of BTC, covering various aspects of epidemiology, diagnosis, and treatment. The 17 clinical questions have important reference value for the management of BTC.
Treatment of Refractory Ascites with Lymphaticovenous Anastomosis Considering Lymphatic Territories
Authors: Nuri Takashi , Asaka Akinori , Ota Mariko , Yae Yuri , Tanaka Yoshimichi , Osuga Keigo , Takashima Shogo , Ohmichi Masahide , Otsuki Yuki , Ueda Koichi
Published: September 2024

Lymphatic ascites is an infrequent complication observed in patients who have undergone lymphadenectomy as part of their surgical treatment for gynecological cancer. Previous research has suggested that intranodal lymphangiography can effectively manage lymphatic leakage. However, its efficacy diminishes for ascites with substantial fluid accumulation. This case report presents a patient who underwent lymphaticovenous anastomosis (LVA) for ascites that was unresponsive to lymphangiography and sclerotherapy. A 70-year-old woman required weekly ascites punctures after surgical treatment of ovarian cancer. Lymphoscintigraphy revealed lymphatic leakage originating from the right pelvic lymphatic vessel. Intranodal lymphangiography was performed from the inferior lateral inguinal region, followed by embolization with 33% NBCA. Despite these measures, recurrence of ascites and lower limb lymphedema were observed. LVA was conducted at 149 days after the primary operation. Before the LVA, indocyanine green was injected into the lateral and medial ankles, first and fourth toe web spaces, and lower abdomen. The indocyanine green lymphography revealed several linear patterns extending from the dorsum of the foot and the lower abdomen to the inguinal lymph node. Among these, the lymphatic vessels leading to the inferior lateral inguinal lymph node were chosen for the LVA. Eight anastomoses were executed at the right thigh, right lower leg, and right lower abdomen. The patient was discharged at 1 day postoperatively. A computed tomography examination conducted at 20 days post-LVA revealed no accumulation of ascites. To improve the success rate of LVA for ascites, a treatment strategy based on lymphatic territories is required.
An Exploratory Study of Dynamic Capabilities and Performance Improvement in Hospitals
Authors: Al-Amin Mona , Sullivan Erin , Szalay Nicole E.
Published: September 2024

Goal:

Recent efforts to push hospitals to provide high-value care have relied on payment incentives. However, evidence indicates that 70% to 90% of performance improvement projects do not achieve their desired goals. Therefore, in addition to managing external industry pressures, hospitals need to develop performance improvement (PI) capabilities that enable them to capitalize on improvement opportunities, effectively develop and adopt solutions, and ensure the sustainability of improvements over time. While operational capabilities enable hospitals to produce and deliver services, more is needed to attain and sustain superior performance. Dynamic capabilities drive changes in operational capabilities to meet environmental demands. Dynamic capabilities also enable hospitals to renew and reconfigure their resources to optimize performance. This paper proposes the dynamic-capabilities framework as an appropriate way to develop and manage PI capabilities in hospitals, and it discusses the implications of shifting to a strategy that is driven by dynamic-capabilities PI.

Methods:

The research team designed a semi-structured interview based on a review of the literature to understand whether hospitals were engaging in the activities outlined in the dynamic-capabilities framework. Nine study participants were recruited from a convenience sample of hospital PI staff at hospitals in Massachusetts and New Hampshire. De-identified transcripts were entered into NVivo12 qualitative data analysis software, and data were thematically indexed and coded following the principles of content analysis.

Principal Findings:

PI structures, improvement methodologies, and weaknesses did not vary significantly among hospitals. Most hospitals had a PI department and were more likely to adopt PI projects initiated by top management. While PI staff were trained in improvement methodologies, no programs were in place that required the rest of the hospital staff to become familiar with PI methods. Common areas of weakness were PI project selection, communication, coordination, learning from current and former PI projects, and systematic approaches to sustain improvements.

Practical Applications:

Dynamic PI capabilities provide an opportunity to systematically identify improvement opportunities, seize on and learn from those opportunities, and renew and reconfigure resources to optimize performance. Ad hoc PI projects are insufficient to enable a hospital to sustain superior performance. Internal and external pressures to deliver high-value patient care and services require hospitals to exceed their current PI efforts. By developing dynamic PI capabilities, hospitals will adopt a more systematic and effective approach to PI, which will likely result in superior performance.
Long-Term Oncologic Outcomes in Patients With Muscle Invasive Bladder Cancer Misclassified as Achieving a Complete Clinical Response to Neoadjuvant Chemotherapy
Authors: Chung Rainjade , Kurtzman Jane T. , Joffe Benjamin I. , Vila-Reyes Helena , Miles Caleb H. , DeCastro Guarionex J. , Anderson Christopher B. , Wei Alexander Z. , Drake Charles G. , McKiernan James M. , Lenis Andrew T.
Published: September 2024

Introduction:

Correctly classifying patients with muscle invasive bladder cancer (MIBC) as achieving a complete clinical response (CCR) to neoadjuvant chemotherapy (NAC) is challenging without radical cystectomy (RC) pathology. The accuracy of clinical staging following NAC is debated, and the risk of occult residual MIBC is real. We present the rate and oncologic outcomes of patients who were misclassified as achieving a CCR to NAC.

Materials and Methods:

We utilized our prospective database of patients who achieved a CCR to NAC and elected active surveillance (AS). Patients with intravesical MIBC within 6 months of CCR classification were defined as potentially misclassified (mCCR). We used Kaplan-Meier curves to assess overall (OS), cancer-specific (CSS), and metastasis-free (MFS) survival and log-rank tests to evaluate differences between cohorts.

Results:

Fifty-four patients, median age of 70 years and follow-up of 49 months, were included. Six patients (11%) were mCCR, and all underwent delayed RC at a mean of 4.3 months after CCR classification. Pre-NAC hydronephrosis was more common in mCCR patients (67% vs 8%, P < .01). Five-year OS, CSS, and MFS for mCCR patients were 63% each, compared with 80%, 89%, and 93%, for the remaining patients. Log-rank tests demonstrated significantly lower OS (P = .03) and MFS (P = .05) in mCCR patients.

Conclusions:

We observed an 11% CCR misclassification rate. While mCCR patients had significantly worse OS and MFS compared with correctly classified CCR patients, we cannot know for certain how survival outcomes would have changed with immediate RC. Our findings are useful when describing the risks of misclassification to CCR patients contemplating AS.
Limited Utility of Quantitative Thresholds on 99mTc-Sestamibi Single-Photon Emission Computed Tomography/Computed Tomography for Distinguishing Renal Cell Carcinoma From Oncocytic Renal Masses
Authors: Wang Robert S. , Yu Jian Q. , Schober Jared , Standiford Taylor , Bell Spencer H. , Doss Mohan , Li Yi , Kutikov Alexander
Published: September 2024

Purpose:

99mTc-sestamibi single-photon emission CT/x-ray CT (SPECT/CT) uses a mitochondria-targeting tracer to differentiate renal cell carcinoma from oncocytomas and hybrid oncocytoma/chromophobe tumors. Initial studies support 99mTc-sestamibi SPECT/CT’s accuracy, but we previously found that oncocytomas still account for 20% of lesions with low tracer uptake in qualitatively interpreted scans. Here, we assess performance of 99mTc-sestamibi SPECT/CT utilizing quantitative assessment thresholds, hypothesizing that this may improve test performance.

Materials and Methods:

All 99mTc-sestamibi SPECT/CT performed for renal mass evaluation between February 2020 and December 2021 was analyzed. A “hot” mass had qualitatively equivalent or higher 99mTc-sestamibi uptake than normal renal parenchyma; a “cold” mass did not. Target-to-background ratios (TBRs) were calculated using tracer counts in the masses vs nearby normal parenchyma. Quantitative “hot”/“cold” determinations were made using published TBR cutoffs. Findings were correlated with histology.

Results:

Seventy-eight patients underwent 99mTc-sestamibi SPECT/CT for 98 renal masses. For the 52 masses with diagnostic pathology, the negative predictive value (NPV) of qualitatively interpreted 99mTc-sestamibi SPECT/CT for ruling out oncocytoma was 80%, with a 1.9% false-positive rate. A TBR cutoff of 0.46 achieved the highest NPV of 89.3%, with a 23.1% false-positive rate. A TBR cutoff of 0.74 achieved the lowest false-positive rate of 1.9%, with a 78.3% NPV. No TBR cutoff achieved both higher NPV and lower false positives than the qualitatively interpreted scans.

Conclusions:

Quantitative TBR cutoffs for interpretation of 99mTc-sestamibi SPECT/CT scans for renal masses do not offer meaningful improvements in accuracy over qualitative reads. Additional studies are required to better characterize the utility of 99mTc-sestamibi SPECT/CT in the real-world setting.
Weight-bearing asymmetry during sit-to-stand after major lower-limb amputation: A systematic review and meta-analysis
Authors: Le Corre Tanguy , Bisseriex Hélène , Pons Christelle , Rémy-Néris Olivier
Published: September 2024

Weight-bearing asymmetry during sit-to-stand (STS) can cause musculoskeletal problems in people with major lower-limb amputation. Does weight-bearing asymmetry differ between individuals with major lower-limb amputation and individuals without amputation? We conducted a systematic review and meta-analysis. We searched PubMed, Cochrane Library, Web of Science, and HAL up to June 2022 using keywords and inclusion/exclusion criteria. Article quality was assessed. Data for population, intervention, weight-bearing asymmetry, and biomechanical analysis were reported. Standardized mean differences (SMDs) were calculated from the outcomes when possible. We included 11 studies (102 people with amputation). Weight-bearing asymmetry was greater in people with amputation than those without amputation (SMD = 1.72 [1.30–2.14] p < 0.00001). It was greater for individuals with transtibial amputation (TTA) and with transfemoral amputation (TFA) than for those without amputation (SMD = 1.20 [0.76–1.65] p < 0.00001 and SMD = 5.32 [4.15–6.50] p < 0.00001, respectively). STS performance time was longer for people with amputation (SMD = 0.52 [0.23–0.81] p = 0.0004) than those without amputation. Trunk motion differed in those with amputation, and lower-limb kinematics differed considerably, especially for people with TFA. Weight-bearing is more asymmetric in people with amputation than in people without amputation. The differences in weight-bearing asymmetry and kinematics during STS between people with TTA and TFA suggest that different strategies are required to improve weight-bearing symmetry: improvements in active prosthetic knees in TFA and rehabilitation focused on weight-bearing in TTA.
Interaction with refuse piles is associated with co-occurrence of core gut microbiota in workers of the ant Aphaenogaster picea
Authors: Pagalilauan Alison , Pavloudi Christina , Ospina Santiago Meneses , Smith Adam , Saw Jimmy
Published: September 2024

Comparing the diversity of gut microbiota between and within social insect colonies can illustrate interactions between bacterial community composition and host behavior. In many eusocial insect species, different workers exhibit different task behaviors. Evidence of compositional differences between core microbiota in different worker types could suggest a microbial association with division of labor among workers. Here we present the core microbiota of Aphaenogaster picea ant workers with different task behaviors. The genus Aphaenogaster is abundant worldwide, yet the associated microbiota of this group is unstudied. Bacterial communities from A. picea gut samples in this study consist of 19 phyla, dominated by Proteobacteria, Cyanobacteria, and Firmicutes. Analysis of 16S rRNA gene sequences reveals distinct similarity clustering of A. picea gut bacterial communities in workers that have more interactions with the refuse piles. Though gut bacterial communities of nurse and foraging ants are similar in overall composition and structure, the worker groups differ in relative abundances of dominant taxa. Gut bacterial communities from ants that have more interactions with refuse piles are dominated by ASVs associated with Entomoplasmataceae. Interaction with fecal matter via refuse piles seems to have the greatest impact on microbial taxa distribution, and this effect appears to be independent of worker type. This is the first report surveying the gut microbiome community composition of Aphaenogaster ants.
Evaluating Physiological Indicators in Detecting Deception and Truthfulness using the Comparison Question Test
Authors: Rashid A M Shahruj , Carmichael Bryan , Su Charlize , Shi Keming , Lim Keefe , Poorvika Senthil Kumar , Wan Ngok Jeun , Govil Eshaan , Yap Dennis
Published: September 2024

Despite significant advancements in deception detection, traditional methods often fall short in real-world applications. This study addresses these limitations by evaluating the effectiveness of various physiological measures — Pupil Response, Electrodermal Activity (EDA), Heart Rate (HR), and facial temperature changes — in predicting deception using the Comparison Question Test (CQT). It also fills a critical research gap by validating these methods within an Asian context. Employing a between-subjects design, data was collected from a diverse sample of 118 participants from Singapore, including Chinese, Indian, and Malay individuals. The research aims to identify which physiological indicators, in combination, offer the most robust predictions of deceptive behavior. Key innovations include the adaptation of the CQT with a modified directed lie paradigm and an expanded sample size to assess the relative importance of each physiological measure. The study’s findings reveal that Pupil Response is the most significant predictor of deception, with EDA enhancing the model’s explanatory power. HR, while relevant, adds limited value when combined with Pupil Response and EDA, and facial temperature changes were statistically non-significant. The study highlights the need for further research into the interactions among physiological measures and their application in varied contexts. This research contributes valuable insights into improving deception detection methodologies and sets the stage for future investigations that could incorporate additional physiological indicators and explore real-world applications.
METTL3 inhibition-activated cGAS/STING axis enhances immunotherapy and PARP inhibitor sensitivity of lung carcinoma
Authors: Zhou Jiawang , He Jiaxin , Lu Yunqing , Yi Cheng , Chang Xing , Tao Lijun , Zhong Ke , Zhang Haisheng , Li Jiexin , Chen Zhuojia , Wang Hongsheng
Published: September 2024

The cGAS/STING-mediated type I interferon response can augment antitumor activity, while the regulatory factors within this innate immune response remain elusive. Herein we found that the RNA m6A methyltransferase METTL3 was upregulated in lung carcinoma tissues. Elevated METTL3 level was correlated with diminished CD8+T cell infiltration and cancer progression in lung carcinoma patients. METTL3 deficiency exacerbated nuclear DNA leakage into the cytoplasm, activating the cGAS pathway and thereby enhancing anti-tumor immunity. Mechanistically, METTL3 deficiency reduced the homologous recombination repair efficacy via downregulation of MSH5, a mutS family protein involved in DNA mismatch repair, leading to increased cytosolic DNA levels. m6A methylation of A2521 ofMSH5stabilized its mRNA via binding with IGF2BP2. On the other hand, m6A methylation of A1545 at the CDS of cGAS decreased mRNA stability and regulates its protein expression. Functionally, knockdown of METTL3 sensitized lung carcinoma cells to the PARP inhibitors.In vivoand clinical data confirmed the positive roles of METTL3 inhibition-activated cGAS/STING axis in tumor growth and lung adenocarcinoma progression. Collectively, METTL3 inhibition activates the cGAS/STING-mediated anti-tumor immunity via induction of cytosolic DNA and cGAS expression, which in turn regulate PARP inhibitor response and cancer progression in lung carcinoma.
Proteome-wide non-cleavable crosslink identification with MS Annika 3.0 reveals the structure of theC. elegansBox C/D complex
Authors: Birklbauer Micha J. , Müller Fränze , Geetha Sowmya Sivakumar , Matzinger Manuel , Mechtler Karl , Dorfer Viktoria
Published: September 2024

Abstract

The field of crosslinking mass spectrometry has seen substantial advancements over the past decades, enabling the structural analysis of proteins and protein-complexes and serving as a powerful tool in protein-protein interaction studies. However, data analysis of large non-cleavable crosslink studies is still a mostly unsolved problem due to itsn-squared complexity. We here introduce a novel algorithm for the identification of non-cleavable crosslinks implemented in our crosslinking search engine MS Annika that is based on sparse matrix multiplication and allows for proteome-wide searches on commodity hardware. Application of this new algorithm enabled us to employ a proteome-wide search ofC. elegansnuclei samples, where we were able to uncover previously unknown protein interactions and conclude a comprehensive structural analysis that provides a detailed view of the Box C/D complex, enhancing our understanding of its assembly and functional dynamics. Our findings provide valuable insights into the intricate regulation of cellular homeostasis and immune responses, which are conserved across species, including humans. Moreover, our algorithm will enable researchers to conduct similar studies that were previously unfeasible.
VHL synthetic lethality screens uncover CBF-β as a negative regulator of STING
Authors: Bertlin James A C , Pauzaite Tekle , Liang Qian , Wit Niek , Williamson James C , Sia Jia Jhing , Matheson Nicholas J , Ortmann Brian M , Mitchell Thomas J , Speak Anneliese O , Zhang Qing , Nathan James A
Published: September 2024

Clear cell renal cell carcinoma (ccRCC) represents the most common form of kidney cancer and is typified by biallelic inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene. Here, we undertake genome-wide CRISPR/Cas9 screening to reveal synthetic lethal interactors ofVHL, and uncover that loss of Core Binding Factor β (CBF-β) causes cell death inVHL-null ccRCC cell lines and impairs tumour establishment and growthin vivo. This synthetic relationship is independent of the elevated activity of hypoxia inducible factors (HIFs) inVHL-null cells, but does involve the RUNX transcription factors that are known binding partners of CBF-β. Mechanistically, CBF-β loss leads to upregulation of type I interferon signalling, and we uncover a direct inhibitory role for CBF-β at theSTINGlocus controlling Interferon Stimulated Gene expression. Targeting CBF-β in kidney cancer both selectively induces tumour cell lethality and promotes activation of type I interferon signalling.
CODE - XAI: Construing and Deciphering Treatment Effects via Explainable AI using Real-world Clinical Data
Authors: Lu Mingyu , Covert Ian , White Nathan J. , Lee Su-In
Published: September 2024

Understanding which features drive the treatment effect has long been a complex and critical question in clinical decision-making. Significant advances have been made in estimating treatment effects, particularly with Conditional Average Treatment Effect (CATE) models. These models account for confounding variables, e.g. age, and gender, thereby capturing heterogeneity in treatment effects. However, identifying the specific features driving these effects remains largely unexplored. To bridge these gaps, we propose CODE-XAI, a framework that interprets CATE models using Explainable AI (XAI) to perform feature discovery. CODE-XAI provides feature attribution at individual and cohort levels, enhancing our understanding of treatment responses. We benchmark these XAI methods using real-world clinical data, demonstrating their effectiveness in uncovering feature contributions and enabling cross-cohort analysis, advancing precision medicine and scientific discovery.
Limited microglial metabolic improvement with time-restricted feeding in diet-induced obesity
Authors: Jiao Han , Jermei Jarne , Liang Xian , van der Zande Hendrik J.P. , Vrieling Frank , Rumanova Valentina Sophia , Dorscheidt Milan , Correa-da-Silva Felipe , Wang Anhui , Foppen Ewout , Arias Alberto Pereira , Stenvers Dirk Jan , Liu Tiemin , Bonger Kimberly , Stienstra Rinke , Zhi Zhang , Kalsbeek Andries , Yi Chun-Xia
Published: September 2024

Time-restricted eating has shown promise for improving metabolic health in obese humans via incompletely resolved mechanisms. In this study, we investigated how time-restricted feeding (TRF) at different times of the day affects microglial immunometabolism using Wistar rats. We found that in high-fat diet (HFD)-fed obese rats, TRF during the active phase reduced fat mass, altered rhythmicity of the microglial transcriptome, and prevented an increase in hypothalamic microglia. These effects were dampened or absent with TRF during the resting phase. However, a HFD-induced microglial immunometabolic phenotype, characterized by reduced electron transport chain and increased lipid metabolism gene expression, and metabolic inflexibility, was not reversed by TRF in either the active or resting phase, indicating that reprogrammed microglial metabolism in obesity is a persistent cellular functional change that requires further study.
Functional Roles of Sensorimotor Alpha and Beta Oscillations in Overt Speech Production
Authors: Huang Lydia Z. , Cao Yang , Janse Esther , Piai Vitória
Published: September 2024

Power decreases, or desynchronization, of sensorimotor alpha and beta oscillations (i.e., alpha and beta ERD) have long been considered as indices of sensorimotor control in overt speech production. However, their specific functional roles are not well understood. Hence, we first conducted a systematic review to investigate how these two oscillations are modulated by speech motor tasks in typically fluent speakers (TFS) and in persons who stutter (PWS). Eleven EEG/MEG papers with source localization were included in our systematic review. The results revealed consistent alpha and beta ERD in the sensorimotor cortex of TFS and PWS. Furthermore, the results suggested that sensorimotor alpha and beta ERD may be functionally dissociable, with alpha related to (somato-)sensory feedback processing during articulation and beta related to motor processes throughout planning and articulation. To (partly) test this hypothesis of a potential functional dissociation between alpha and beta ERD, we then analyzed existing intracranial electroencephalography (iEEG) data from the primary somatosensory cortex (S1) of picture naming. We found moderate evidence for alpha, but not beta, ERD’s sensitivity to speech movements in S1, lending supporting evidence for the functional dissociation hypothesis identified by the systematic review.
The Rapid Online Cognitive Assessment
Authors: Howard Calvin W. , Johnson Amy , Peedicail Joseph , Ng Marcus
Published: September 2024

INTRODUCTION

Paper-based screening examinations are well-validated but minimally scalable. If a DCA replicate paper-based screening, it would improve scalability while benefiting from their extensive validation.

METHODS

We developed and evaluated the Rapid Online Cognitive Assessment (RoCA) against gold-standard paper-based tests in patients with a range of cognitive integrity (n = 46). Patient perception of the RoCA was also evaluated with post-examination survey.

RESULTS

The RoCA classifies patients similarly to gold standard paper-based tests, with a receiver operating characteristic area under the curve of 0.81 (95%CI 0.67-0.91, p < 0.001). It achieves a sensitivity of 0.94 (95%CI 0.80-1.0, p < 0.001). This was robust to multiple control analyses. 83% of patient respondents reported the RoCA as highly intuitive, with 95% perceiving it as adding value to their care.

DISCUSSION

The RoCA may act as a simple and highly scalable cognitive screen.
Dissociable dynamic effects of expectation during statistical learning
Authors: McDermott Hannah H. , De Martino Federico , Schwiedrzik Caspar M. , Auksztulewicz Ryszard
Published: September 2024

The brain is thought to generate internal predictions, based on previous statistical regularities in the environment, to optimise behaviour. Predictive processing has been repeatedly demonstrated and seemingly explains expectation suppression (ES), or the attenuation of neural activity in response to expected stimuli. However, the mechanisms behind ES are unclear and various models of the mechanisms supporting ES have been suggested with conflicting evidence. Sharpening models propose that expectations suppress neurons that are not tuned to the expected stimulus, increasing the signal-to-noise ratio for expected stimuli. In contrast, dampening models posit that expectations suppress neurons that are tuned to the expected stimuli, increasing the relative response amplitude for unexpected stimuli. Previous studies have used decoding analyses to examine these effects, with increases in decoding accuracy interpreted in terms of sharpening and decreases related to dampening. The opposing process theory (OPT) has suggested that both processes may occur at different time points, namely that initial sharpening is followed by later dampening of the neural representations of the expected stimulus as learning progresses. In this study we aim to test this theory and shed light on the dynamics of expectation effects, both at single trial level and over time. Thirty-one participants completed a statistical learning task consisting of paired scene categories whereby a “leading” image from one category is quickly followed by a “trailing” image from a different category. Multivariate EEG analyses focussed on decoding stimulus information related to the trailing image category. Within-trial, decoding analyses showed that stimulus expectation increased decoding accuracy at early latencies and decreased decoding accuracy at later latencies, in line with OPT. However, across trials, stimulus expectation decreased decoding accuracy in initial trials and increased decoding accuracy in later trials. We theorise that these dissociable dynamics of expectation effects within and across trials can be explained in the context of hierarchical learning mechanisms. Our single trial results provide evidence for the OPT, while our results over time suggest that sharpening and dampening effects emerge at different stages of learning.
A Distinct Alternative mRNA Splicing Profile Identifies the Oncogenic CD44 Transcript Variant 3 in KMT2A-Rearranged Pediatric T-cell Acute Lymphoblastic Leukemia Cells
Authors: Amor Amanda Ramilo , Enlund Sabina , Sinha Indranil , Jiang Qingfei , Hermanson Ola , Nilsson Anna , Shirazi Fard Shahrzad , Holm Frida
Published: September 2024

T-cell acute lymphoblastic leukemia (T-ALL), which constitutes of 10-15% of all pediatric ALL cases, is known for its complex pathology due to pervasive genetic and chromosomal abnormalities. Although most children are successfully cured, chromosomal rearrangements involving the KMT2A (KMT2A) gene is considered a poor prognostic factor. In a cohort of 171 pediatric T-ALL samples we have studied differences in gene and splice variant patterns in KMT2A rearranged (KMT2A-r) T-ALL compared to KMT2A negative (KMT2A-wt) T-ALL samples. Our results have identified a distinct gene expression and splice variant expression pattern in pediatric KMT2A-r patient samples including significant expression of splicing regulatory markers ESRP1 and MBNL3. Additionally, the pro-survival long transcript variant of BCL2 were upregulated in KMT2A-r compared to KMT2A-wt T-ALL samples. Lastly, increased levels of activating methylation in the promoter region of CD44 were identified followed by an upregulation of the oncogenic transcript variant CD44v3 in KMT2A-r T-ALL. Together this suggests that CD44v3 could play a potential role as gene expression-based risk stratification of KMT2A-r rearranged T-ALL and could possibly serve as a therapeutic target using splicing modulators.