bluuebunny/crossref_metadata_2025 huggingface dataset:
Fixation of transverse midshaft clavicle fractures with nitinol staples vs. superior locked plating: a biomechanical study
Authors: Mistretta Katherine L. , Abbasi Pooyan , Wright Melissa A. , Murthi Anand M.
Published: May 2023

Background:

Nitinol staples have been used effectively for stabilization and compression at fracture sites. This study compared yield load, fracture displacement, and load to failure between nitinol staples and superior plating for midshaft clavicle fractures.

Methods:

Ten pairs of cadaveric clavicles underwent midshaft osteotomy. Each specimen in each pair was randomly assigned to fixation with superiorly placed nitinol staples or with superior plating. Specimens were loaded cyclically with increasing loads to a maximum of 1200 cycles and 60 N. Fracture displacement and construct stiffness were compared at each load. Load to failure was performed at the conclusion of testing.

Results:

The staple group demonstrated lower yield load and higher median fracture displacement at all levels of force compared to the plate group. Median displacement at physiologic load was 15.3 (IQR 12.8-16.5) mm for the staple construct and 2.9 (IQR 2.5-3.6) mm for plated constructs (P=2.04E-07). Median stiffness of plated constructs was significantly higher than staple constructs at all levels (P<0.05). Median cycles to failure for staple constructs was significantly lower compared to plated constructs (P=0.004). Median load to failure was significantly higher for plated constructs compared to staple constructs (P=2.8E-06).

Conclusions:

Nitinol staple fixation of midshaft clavicle fractures demonstrated lower yield load, stiffness, increased displacement, and lower load to failure compared to superior plate fixation. However, staple constructs provided adequate stability to maintain reduction of the fracture at physiologic levels of repetitive stress, indicating a potential role for nitinol staples in clavicle fracture fixation.
Progress in the surgical treatment of sacrococcygeal pilonidal sinus: a review
Authors: Wu Peiliang , Zhang Yingyi , Zhang Yewei , Wang Shuang , Fan Zhe
Published: May 2023

Background:

A pilonidal sinus (PS) is an acquired disease resulting from recurrent infections and chronic inflammation. A PS involving the sacrococcyx is referred to as a sacrococcygeal PS (SPS). An SPS is a rare chronic infectious disease for which surgery is a good choice. The incidence of SPS has gradually increased worldwide in recent years. However, surgeons have not reached a consensus on the preferred surgical approach for SPS. The authors performed a systematic review and meta-analysis to analyze differences in the efficacy of different surgical approaches for the treatment of SPS.

Methods:

A systematic search was conducted in the PubMed database covering the period from 1 January 2003, to 28 February 2023. The primary outcome parameters were recurrence and infection. Finally, statistical analysis (meta-analysis) was carried out using RevMan 5.4.1 software. In addition, we systematically reviewed the latest progress in the surgical treatment of SPS over the past 20 years, especially as reported in the past 3 years.

Results:

Twenty-seven articles, 54 studies, and 3612 participants were included in this meta-analysis. The recurrence rate following the midline closure (MC) technique was much higher than that of other techniques. Among the techniques analyzed, the differences between MC and Limberg flap (LF), and between MC and marsupialization were statistically significant [P=0.0002, risk ratio (RR)=6.15, 95% CI 2.40, 15.80; P=0.01, RR=12.70, 95% CI 1.70, 95.06]. The recurrence rate of open healing was higher than that of the Karydakis flap (KF) technique, and the difference was statistically significant (P=0.02, RR=6.04, 95% CI 1.37, 26.55). Most of the results comparing MC with other techniques suggested that the former had a higher infection rate, and the difference between MC and LF was statistically significant (P=0.0005, RR=4.14, 95% CI 1.86, 9.23). Comparison between KF and LF, modified LF and KF showed that the differences were not statistically significant in terms of recurrence and infection (P≥0.05).

Conclusions:

There are various surgical treatment options for SPS, including incision and drainage, excision of diseased tissue with primary closure and secondary healing, and minimally invasive surgery. It is still not possible to determine which surgical technique should be considered the gold standard for treatment, as even the results of different researchers using the same operation method are conflicting. But what is certain is that the midline closure technique has a much higher incidence of postoperative recurrence and infection than other techniques. Therefore, the anorectal surgeon should formulate the most suitable individualized plan for the patient based on a comprehensive evaluation of the patient’s wishes, appearance of the SPS, and the professional ability of the surgeon.
Home monitoring of coronavirus disease 2019 patients in different phases of disease
Authors: Majoor Kalle , Vorselaars Adriane D.M.
Published: May 2023

Purpose of review

Various home monitoring programs have emerged through the COVID-19 pandemic in different phases of COVID-19 disease.

Recent findings

The prehospital monitoring of COVID-19-positive patients detects early deterioration. Hospital care at home provides early discharge with oxygen to empty hospital beds for other patients. Home monitoring during recovery can be used for rehabilitation and detection of potential relapses. General goals of home monitoring in COVID-19 are early detection of deterioration and prompt escalation of care such as emergency department presentation, medical advice, medication prescription and mental support. Due to the innovations of vaccination and treatment changes, such as dexamethasone and tocilizumab, the challenge for the healthcare system has shifted from large numbers of admitted COVID-19 patients to lower numbers of admitted patients with specific risk profiles (such as immunocompromised). This also changes the field of home monitoring in COVID-19. Efficacy and cost-effectiveness of home monitoring interventions depend on the costs of the intervention (use of devices, apps and medical staff) and the proposed patient group (depending on risk factors and disease severity).

Patient satisfaction of COVID-19 home monitoring programs was mostly high. Home monitoring programs for COVID-19 should be ready to be re-escalated in case of a new global pandemic.
Clinical utility of somatostatin receptor positron emission tomography imaging biomarkers for characterization of meningioma among incidental central nervous system lesions
Authors: Ensign Shannon Fortin , Agarwal Muskan , Klanderman Molly , Badawy Mohamed , Halfdanarson Thorvardur R. , Johnson Derek R. , Sonbol Mohamad Bassam , Kendi Ayse T.
Published: May 2023

Objectives

Somatostatin receptor (SSTR) PET imaging is utilized with increasing frequency in the clinical management of neuroendocrine tumors. Incidental PET-avid CNS lesions are commonly noted and presumed to be meningiomas. However, SSTR PET lacks specificity for meningioma identification. This study aimed to clarify the role of SSTR-based imaging in the classification of incidental CNS lesions based on current clinical practice.

Methods

Patients who underwent both Ga-68-DOTATATE PET and brain MRI and had an incidental CNS lesion identified with a radiographic prediction of meningioma via one (discordant prediction) or both (concordant prediction) imaging modalities were retrospectively analyzed. Imaging indication, semiquantitative measures, and clinical history were recorded.

Results

Among 48 patients with a CNS lesion identified on both imaging modalities, most scans were performed for a history of neuroendocrine tumor (64.6%). Cases with concordant lesion-type prediction of meningioma between imaging modalities (N = 24) displayed a significantly higher SUV max (median 7.9 vs. 4.0; P = 0.008) and Krenning score (median 3.0 vs. 2.0; P = 0.005) on Ga-68-DOTATATE PET compared with cases with a discordant prediction of meningioma (N = 24). In cases with lower SUV max values, Ga-68-DOTATATE was more likely to discordantly predict meningioma without agreement by the corresponding MRI. Prior cranial radiation or use of somatostatin mimetics did not affect quantitative radiographic measures, and MRI-based tumor size was similar across groups.

Conclusion

Lesions with increased avidity may be more confidently predicted as meningioma in Ga-68-DOTATATE PET scans, whereas there is more discrepancy in prediction among low SUV cases.
Evolution and current applications of endoscopic combined intrarenal surgery: a scoping review from back to the future
Authors: Gauhar Vineet , Traxer Olivier , Fuligni Demetra , Brocca Carlo , Galosi Andrea Bendetto , Teoh Jeremy Yuen-Chun , Castellani Daniele
Published: May 2023

Purpose of review

To systematically review the evolution of techniques, technology, clinical utility, limitations and possible future applications of endoscopic combined intrarenal surgery (ECIRS) for ureteral and kidney stones.

Recent findings

The literature search was performed on 18th January 2023 using PubMed, EMBASE and Scopus. 35 studies were included. Among them, six were reviews. Since its introduction in 2008, ECIRS has evolved and improved. ECIRS can be performed in different patient position, such as modified supine Valdivia position by Galdakao, prone position with split-leg and supine position with good outcomes. Instrument miniaturization has also been introduced in ECIRS making it doable in an ambulatory setting. ECIRS showed shorter operative time, lower complication rate, and retreatment compared with conventional PCNL. Operative outcomes of mini-ECIRS are better than mini-PCNL alone. ECIRS also showed good outcomes in impacted upper ureteric stones. Recently, some studies have explored the robotic-assisted kidney puncture in ECIRS that avoided multitrack surgery, especially in anomalous kidney and staghorn stones.

ECIRS is ready for primetime in endourology and can be considered the next gold-standard for a personalized stone approach in complex kidney stones.
Genetics of the rabbit haemorrhagic disease virus strains responsible for rabbit haemorrhagic disease outbreaks in Japan between 2000 and 2020
Authors: Tanikawa Taichiro , Watanabe Satoko , Mikami Osamu , Miyazaki Ayako
Published: May 2023

Rabbit haemorrhagic disease (RHD) is a highly contagious and fatal disease in rabbits caused by the rabbit haemorrhagic disease virus (RHDV), which includes two genotypes, RHDV-GI.1 and RHDV2-GI.2. RHDVs tend to recombine among different strains, resulting in significant genetic evolution. This study evaluated the genetics of Japanese RHDV strains associated with six outbreaks between 2000 and 2020 using whole-genome sequencing, genomic recombination and phylogenetic analyses. Genomic recombination analysis using near-complete genomic sequences revealed that two Japanese strains detected in 2000 and 2002 were non-recombinant GI.1 (variant RHDVa-GI.1a) strains of different origins, most closely related to strains identified in PR China in 1997 and the USA in 2001, respectively. In contrast, four recent Japanese GI.2 strains detected between 2019 and 2020 were recombinant viruses harbouring structural protein (SP) genes from GI.2 strains and non-SP (NSP) genes from a benign rabbit calicivirus (RCV) strain of genotype RCV-E1-GI.3 (GI.3P–GI.2) or an RHDV G1-GI.1b variant (GI.1bP–GI.2). Phylogenetic analysis based on SP and NSP regions revealed that the GI.1bP–GI.2 recombinant virus detected in Ehime prefecture and the GI.3P–GI.2 recombinant viruses detected in Ibaraki, Tochigi and Chiba prefectures were most closely related to recombinant viruses identified in Australia in 2017 and Germany in 2017, respectively. These results suggested that past RHD outbreaks in Japan did not result from the evolution of domestic RHDVs but rather represented incursions of foreign RHDV strains, implying that Japan is constantly at risk of RHDV incursion from other countries.
Nonviral PDMAEMA Vectors Efficiently Express PDE6β in a Mouse Model of Retinitis Pigmentosa
Authors: Bitoque Diogo B. , Calado Sofia M. , Rosa da Costa Ana M. , Silva Gabriela A.
Published: May 2023

Retinitis Pigmentosa (RP) is one of main causes of inherited blindness, with about 6% of cases caused by a single mutation in the PDE6β gene, making it an ideal candidate for a gene therapy intervention. Gene therapy has been shown to restore normal retinal and visual function in other monogenic diseases, such as Lebers’ Congenital Amaurosis and choroideremia, and RP could benefit from a similar therapeutic approach.

Our goal was to combine efficient nonviral vectors and gene expression systems to express the PDE6β gene in the retina of a mouse model of Retinitis Pigmentosa. We have firstly validated the potential of PDMAEMA polyplexes as a nonviral vector by subretinal injection, which were shown to efficiently promote gene expression in the RPE layer of the adult mouse retina. We have then produced polyplexes of PDMAEMA with a replicating plasmid expressing the PDE6β gene and administered the polyplexes via subretinal injection in the rd10 mouse. We have observed that PDMAEMA polyplexes were able to efficiently enter the target retinal pigment epithelium cells and rapidly express the PDE6β gene in the mouse retina, thus confirming their potential as nonviral vectors for retinal gene therapy.
Anti-tau antibodies targeting a conformation-dependent epitope selectively bind seeds
Authors: Hitt Brian D. , Gupta Ankit , Singh Ruhar , Yang Ting , Beaver Joshua D. , Shang Ping , White Charles L. , Joachimiak Lukasz A. , Diamond Marc I.
Published: May 2023

Neurodegenerative tauopathies are caused by transition of tau protein from a monomer to a toxic aggregate. They include Alzheimer disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and Pick disease (PiD). We have previously proposed that tau monomer exists in two conformational ensembles: an inert form (Mi), which does not self-assemble; and seed-competent form (Ms), which self-assembles and templates ordered assembly growth. We proposed that cis/trans isomerization of tau at P301, the site of dominant disease-associated S/L mis-sense mutations, might underlie the transition of wild-type tau to a seed-competent state. Consequently, we created monoclonal antibodies using non-natural antigens consisting of fluorinated proline (P*) at the analogous P270 in R1, biased towards the trans-configuration at either the R1/R2 (TENLKHQP*GGGKVQIINKK) or R1/R3 (TENLKHQP*GGGKVQIVYK) interfaces. Two antibodies, MD2.2 and MD3.1 efficiently immunoprecipitated soluble seeds from AD and PSP, but not CBD or PiD. They stained brain samples of AD, PSP, and PiD, but not CBD. They did not immunoprecipitate, or immunostain tau from control brain. Creation of potent anti-seed antibodies based on the trans-proline epitope implicates local unfolding around P301 in pathogenesis. MD2.2 and MD3.1 may also be useful for therapy and diagnosis.

Tau protein undergoes conformational change to self-assemble and trigger neurodegeneration. We have proposed local unfolding events centered on P301 cis/trans isomerization, which expose amyloidogenic sequences. We used a non-natural peptide with a trans-proline to generate monoclonal antibodies that distinguish tau seeds from native tau in human brain. In addition to being important therapeutic and diagnostic leads, the activity of these antibodies supports structural studies implicating local conformational change in tau that underlies disease initiation.
Unveiling the role of osteosarcoma-derived secretome in premetastatic lung remodelling
Authors: Almeida Sara F.F. , Santos Liliana , Ribeiro Gabriela , Ferreira Hugo R.S. , Lima Nuno , Caetano Rui , Abreu Mónica , Zuzarte Mónica , Ribeiro Ana Sofia , Paiva Artur , Martins-Marques Tânia , Teixeira Paulo , Almeida Rui , Manuel Casanova José , Girão Henrique , Abrunhosa Antero J. , Gomes Célia M.
Published: May 2023

Lung metastasis represents the leading cause of osteosarcoma-related death. Progress in preventing lung metastasis is pretty modest due to the inherent complexity of the metastatic process and the lack of suitable models. Herein, we provide mechanistic insights into how osteosarcoma systemically reprograms the lung microenvironment for metastatic outgrowth using metastatic mouse models and a multi-omics approach.

We found that osteosarcoma-bearing mice or those preconditioned with cell-secretome harbour profound lung structural alteration with airways damage, inflammation, neutrophil infiltration, and remodelling of the extracellular matrix with deposition of fibronectin and collagen by stromal activated fibroblasts for tumour cell adhesion. These changes, supported by transcriptomic and histological data, promoted and accelerated the development of lung metastasis. Comparative proteome profiling of the cell secretome and mouse plasma identified a large number of proteins engaged in the extracellular-matrix organization, cell-matrix adhesion, neutrophil degranulation, and cytokine-mediated signalling, which were consistent with the observed lung microenvironmental changes. Moreover, we identified EFEMP1, a secreted extracellular matrix glycoprotein, as a potential risk factor for lung metastasis and a poor prognosis factor in osteosarcoma patients.
Omicron Spike confers enhanced infectivity and interferon resistance to SARS-CoV-2 in human nasal tissue
Authors: Shi Guoli , Li Tiansheng , Lai Kin Kui , Johnson Reed F. , Yewdell Jonathan W , Compton Alex A
Published: May 2023

Omicron emerged following COVID-19 vaccination campaigns, displaced previous SARS-CoV-2 variants of concern worldwide, and gave rise to lineages that continue to spread. Here, we show that Omicron exhibits increased infectivity in primary adult upper airway tissue relative to Delta. Using recombinant forms of SARS-CoV-2 and nasal epithelial cells cultured at the liquid-air interface, enhanced infectivity maps to the step of cellular entry and evolved recently through mutations unique to Omicron Spike. Unlike earlier variants of SARS-CoV-2, Omicron enters nasal cells independently of serine transmembrane proteases and instead relies upon metalloproteinases to catalyze membrane fusion. This entry pathway unlocked by Omicron Spike enables evasion of constitutive and interferon-induced antiviral factors that restrict SARS-CoV-2 entry following attachment. Therefore, the increased transmissibility exhibited by Omicron in humans may be attributed not only to its evasion of vaccine-elicited adaptive immunity, but also to its superior invasion of nasal epithelia and resistance to the cell-intrinsic barriers present therein.
Stability of dentate gyrus granule cell mossy fiber BDNF protein expression with age and resistance of granule cells to Alzheimer’s disease neuropathology in a mouse model
Authors: Criscuolo Chiara , Chartampila Elissavet , Ginsberg Stephen D. , Scharfman Helen E.
Published: May 2023

The neurotrophin brain-derived neurotrophic factor (BDNF) is important in development and maintenance of neurons and their plasticity. Hippocampal BDNF has been implicated Alzheimer’s disease (AD) because hippocampal levels in AD patients and AD animal models are consistently downregulated, suggesting that reduced BDNF contributes to AD. However, the location where hippocampal BDNF protein is most highly expressed, the mossy fiber (MF) axons of dentate gyrus (DG) granule cells (GCs), has been understudied, and never in controlledin vivoconditions. We examined MF BDNF protein in the Tg2576 mouse model of AD. Tg2576 and wild type (WT) mice of both sexes were examined at 2-3 months of age, when amyloid-β (Aβ) is present in neurons but plaques are absent, and 11-20 months of age, after plaque accumulation. As shown previously, WT mice exhibited high levels of MF BDNF protein. Interestingly, there was no significant decline with age in either genotype or sex. Notably, we found a correlation between MF BDNF protein and GC ΔFosB, a transcription factor that increases after 1-2 weeks of elevated neuronal activity. Remarkably, there was relatively little evidence of Aβ in GCs or the GC layer even at old ages. Results indicate MF BDNF is stable in the Tg2576 mouse, and MF BDNF may remain unchanged due to increased GC neuronal activity, since BDNF expression is well known to be activity-dependent. The resistance of GCs to long-term Aβ accumulation provides an opportunity to understand how to protect other vulnerable neurons from increased Aβ levels and therefore has translational implications.

SIGNIFICANCE

Declining hippocampal brain-derived neurotrophic factor (BDNF) has been implicated in the pathogenesis of Alzheimer’s disease (AD). However, few studies have examined where hippocampal BDNF protein has its highest concentration, and plays a critical role in memory, the dentate gyrus granule cell (GC) axons (mossy fibers; MFs). Using a well-established mouse model of cerebral amyloid overexpression, the Tg2576 mouse model of AD, we found that MF BDNF did not decline with age, suggesting a notable exception to the idea that reduced hippocampal BDNF contributes to AD pathobiology. We also identified that Tg2576 GC activity correlates with MF BDNF protein based on GC expression of the transcription factor ΔFosB. These data are consistent with the activity-dependence of MF BDNF. In addition, we found that Tg2576 GCs were relatively resistant to accumulation of amyloid-b, providing insight into AD resilience, which has strong therapeutic implications.
Lateralized Neural Entropy modulates with Grip Force during Precision Grasping
Authors: Rao Nishant , Paek Andrew , Contreras-Vidal Jose L. , Parikh Pranav J.
Published: May 2023

When holding a coffee mug filled to the brim, we strive to avoid spilling the coffee. This ability relies on the neural processes underlying the control of finger forces on a moment-to-moment basis. The brain activity lateralized to the contralateral hemisphere averaged over a trial and across the trials is known to be associated with the magnitude of grip force applied on an object. However, the mechanistic involvement of the variability in neural signals during grip force control remains unclear. In this study, we examined the dependence of neural variability over the frontal, central, and parietal regions assessed using noninvasive electroencephalography (EEG) on grip force magnitude during an isometric force control task. We hypothesized laterally specific modulation in EEG variability with higher magnitude of the grip force exerted during grip force control. We utilized an existing EEG dataset (64 channel) comprised of healthy young adults, who performed an isometric force control task while receiving visual feedback of the force applied. The force magnitude to be exerted on the instrumented object was cued to participants during the task, and varied pseudorandomly among 5, 10, and 15% of their maximum voluntary contraction (MVC) across the trials. We quantified neural variability via sample entropy (sequence-dependent measure) and standard deviation (sequence-independent measure) of the temporal EEG signal over the frontal, central, and parietal electrodes. The EEG sample entropy over the central electrodes showed lateralized, nonlinear, localized, modulation with force magnitude. Similar modulation was not observed over frontal or parietal EEG activity, nor for standard deviation in the EEG activity. Our findings highlight specificity in neural control of grip forces by demonstrating the modulation in sequence-dependent but not sequence-independent component of EEG variability. This modulation appeared to be lateralized, spatially constrained, and functionally dependent on the grip force magnitude. We discuss the relevance of these findings in scenarios where a finer precision is essential to enable grasp application, such as prosthesis and associated neural signal integration, and propose directions for future studies investigating the mechanistic role of neural entropy in grip force control.
Inferring Alzheimer’s disease pathologic traits from clinical measures in living adults
Authors: Yang Jingjing , Liu Xizhu , Oveisgharan Shahram , Zammit Andrea R. , Nag Sukriti , Bennett David A , Buchman Aron S
Published: May 2023

Background

Alzheimer’s disease neuropathologic changes (AD-NC) are important for identify people with high risk for AD dementia (ADD) and subtyping ADD.

Objective

Develop imputation models based on clinical measures to infer AD-NC.

Methods

We used penalized generalized linear regression to train imputation models for four AD-NC traits (amyloid-β, tangles, global AD pathology, and pathologic AD) in Rush Memory and Aging Project decedents, using clinical measures at the last visit prior to death as predictors. We validated these models by inferring AD-NC traits with clinical measures at the last visit prior to death for independent Religious Orders Study (ROS) decedents. We inferred baseline AD-NC traits for all ROS participants at study entry, and then tested if inferred AD-NC traits at study entry predicted incident ADD and postmortem pathologic AD.

Results

Inferred AD-NC traits at the last visit prior to death were related to postmortem measures withR2=(0.188,0.316,0.262) respectively for amyloid-β, tangles, and global AD pathology, and prediction Area Under the receiver operating characteristic Curve (AUC) 0.765 for pathologic AD. Inferred baseline levels of all four AD-NC traits predicted ADD. The strongest prediction was obtained by the inferred baseline probabilities of pathologic AD with AUC=(0.919,0.896) for predicting the development of ADD in 3 and 5 years from baseline. The inferred baseline levels of all four AD-NC traits significantly discriminated pathologic AD profiled eight years later with p-values<1.4 × 10−10.

Conclusion

Inferred AD-NC traits based on clinical measures may provide effective AD biomarkers that can estimate the burden of AD-NC traits in aging adults.
Does targeted memory reactivation during NREM sleep require complementary REM sleep for memory consolidation?
Authors: Sifuentes Ortega Rebeca , Simor Péter , Peigneux Philippe
Published: May 2023

Presentation of learning-related cues during NREM sleep has been shown to improve memory consolidation. Past studies suggest that REM sleep may contribute to the beneficial effect of reactivating memories during NREM sleep, but the relationship between REM sleep and induced reactivations in NREM remains unclear. We investigated whether a naturally ensuing episode of REM sleep is necessary for prior NREM targeted memory reactivation (TMR) to exert a beneficial effect on memory consolidation. Nineteen participants learned the association between prior or non-prior known objects and their names (pseudowords) in a within-subject multiple session experiment, in which TMR was subsequently performed either before (Pre-REM) or after (Post-REM) the final REM sleep episode of the night. While word-picture association recall measures did not differ between TMR conditions, we found better name recognition based on confidence ratings for words reactivated during Pre-REM TMR in contrast with associations cued during Post-REM TMR. In addition, we found distinct associations between cue-evoked sigma activity, subsequent REM theta power and TMR memory benefits which were contingent upon the level of relatedness with prior knowledge for the learned material. Although TMR may be less effective during the second half of the night, our findings suggest an interplay between NREM and REM sleep oscillatory activity for memory reactivation and consolidation processes.
Crucial neuroprotective roles of the metabolite BH4 in dopaminergic neurons
Authors: Cronin Shane J. F. , Yu Weonjin , Hale Ashley , Licht-Mayer Simon , Crabtree Mark J , Korecka Joanna A. , Tretiakov Evgenii O. , Sealey-Cardona Marco , Somlyay Mate , Onji Masahiro , An Meilin , Fox Jesse D. , Turnes Bruna Lenfers , Gomez-Diaz Carlos , da Luz Scheffer Débora , Cikes Domagoj , Nagy Vanja , Weidinger Adelheid , Wolf Alexandra , Reither Harald , Chabloz Antoine , Kavirayani Anoop , Rao Shuan , Andrews Nick , Latremoliere Alban , Costigan Michael , Douglas Gillian , Freitas Fernando Cini , Pifl Christian , Walz Roger , Konrat Robert , Mahad Don J. , Koslov Andrey V. , Latini Alexandra , Isacson Ole , Harkany Tibor , Hallett Penelope J. , Bagby Stefan , Woolf Clifford J. , Channon Keith M. , Je Hyunsoo Shawn , Penninger Josef M.
Published: May 2023

Dopa-responsive dystonia (DRD) and Parkinson’s disease (PD) are movement disorders caused by the dysfunction of nigrostriatal dopaminergic neurons. Identifying druggable pathways and biomarkers for guiding therapies is crucial due to the debilitating nature of these disorders. Recent genetic studies have identified variants of GTP cyclohydrolase-1 (GCH1), the rate-limiting enzyme in tetrahydrobiopterin (BH4) synthesis, as causative for these movement disorders. Here, we show that genetic and pharmacological inhibition of BH4 synthesis in mice and human midbrain-like organoids accurately recapitulates motor, behavioral and biochemical characteristics of these human diseases, with severity of the phenotype correlating with extent of BH4 deficiency. We also show that BH4 deficiency increases sensitivities to several PD-related stressors in mice and PD human cells, resulting in worse behavioral and physiological outcomes. Conversely, genetic and pharmacological augmentation of BH4 protects mice from genetically- and chemically induced PD-related stressors. Importantly, increasing BH4 levels also protects primary cells from PD-affected individuals and human midbrain-like organoids (hMLOs) from these stressors. Mechanistically, BH4 not only serves as an essential cofactor for dopamine synthesis, but also independently regulates tyrosine hydroxylase levels, protects against ferroptosis, scavenges mitochondrial ROS, maintains neuronal excitability and promotes mitochondrial ATP production, thereby enhancing mitochondrial fitness and cellular respiration in multiple preclinical PD animal models, human dopaminergic midbrain-like organoids and primary cells from PD-affected individuals. Our findings pinpoint the BH4 pathway as a key metabolic program at the intersection of multiple protective mechanisms for the health and function of midbrain dopaminergic neurons, identifying it as a potential therapeutic target for PD.
Enhancing Collaborative Neuroimaging Research: Introducing COINSTAC Vaults for Federated Analysis and Reproducibility
Authors: Martin Dylan , Basodi Sunitha , Panta Sandeep , Rootes-Murdy Kelly , Prae Paul , Sarwate Anand D. , Kelly Ross , Romero Javier , Baker Bradley T. , Gazula Harshvardhan , Bockholt Jeremy , Turner Jessica , Esper Nathalia B. , Franco Alexandre R. , Plis Sergey , Calhoun Vince D.
Published: May 2023

Collaborative neuroimaging research is often hindered by technological, policy, administrative, and methodological barriers, despite the abundance of available data. COINSTAC is a platform that successfully tackles these challenges through federated analysis, allowing researchers to analyze datasets without publicly sharing their data. This paper presents a significant enhancement to the COINSTAC platform: COINSTAC Vaults (CVs). CVs are designed to further reduce barriers by hosting standardized, persistent, and highly-available datasets, while seamlessly integrating with COINSTAC’s federated analysis capabilities. CVs offer a user-friendly interface for self-service analysis, streamlining collaboration and eliminating the need for manual coordination with data owners. Importantly, CVs can also be used in conjunction with open data as well, by simply creating a CV hosting the open data one would like to include in the analysis, thus filling an important gap in the data sharing ecosystem. We demonstrate the impact of CVs through several functional and structural neuroimaging studies utilizing federated analysis showcasing their potential to improve the reproducibility of research and increase sample sizes in neuroimaging studies.
RNase H genes cause distinct impacts on RNA:DNA hybrid formation and mutagenesis genome-wide
Authors: Schroeder Jeremy W. , Hurto Rebecca L. , Randall Justin R. , Wozniak Katherine J. , Timko Taylor A. , Nye Taylor M. , Wang Jue D. , Freddolino Peter L. , Simmons Lyle A.
Published: May 2023

RNA:DNA hybrids such as R-loops affect genome integrity and DNA replication fork progression. The overall impacts of naturally occurring RNA:DNA hybrids on genome integrity, and the relative contributions of ribonucleases H to mitigating the negative effects of hybrids, remain unknown. Here, we investigate the contributions of RNases HII (RnhB) and HIII (RnhC) to hybrid removal, DNA replication, and mutagenesis genome-wide. Deletion of eitherrnhBorrnhCtriggers RNA:DNA hybrid accumulation, but with distinct patterns of mutagenesis and hybrid accumulation. Across all cells, hybrids accumulate most strongly in non-coding RNAs and 5′-UTRs of coding sequences. For ΔrnhB, hybrids accumulate preferentially in untranslated regions and early in coding sequences. Hybrid accumulation is particularly sensitive to gene expression in ΔrnhC; in cells lacking RnhC, DNA replication is disrupted leading to transversions and structural variation. Our results resolve the outstanding question of how hybrids in native genomic contexts interact with replication to cause mutagenesis and shape genome organization.
Prior context and individual alpha frequency (IAF) influence predictive processing during language comprehension
Authors: Jano Sophie , Cross Zachariah , Chatburn Alex , Schlesewsky Matthias , Bornkessel-Schlesewsky Ina
Published: May 2023

The extent to which the brain predicts upcoming information during language processing remains controversial. To shed light on this debate, the present study reanalysed Nieuwland and colleagues’ (2018) replication of DeLong et al. (2005). Participants (N= 356) viewed sentences containing articles and nouns of varying predictability, while their electroencephalogram was recorded. We measured event-related potentials (ERPs) preceding the critical words (namely the semantic prediction potential; SPP), in conjunction with post-word N400 patterns and individual neural metrics. ERP activity was compared with two measures of word predictability: cloze probability and lexical surprisal. In contrast to prior literature, SPP amplitudes did not increase as cloze probability increased, suggesting that the component may not reflect prediction during natural language processing. Initial N400 results at the article provided evidence against phonological prediction in language, in line with Nieuwland and colleagues’ findings. Strikingly however, when the surprisal of the prior words in the sentence was included in the analysis, increases in article surprisal were associated with increased N400 amplitudes, consistent with prediction accounts. This relationship between surprisal and N400 amplitude was not observed when the surprisal of the two prior words was low, suggesting that expectation violations at the article may be overlooked under highly predictable conditions. Individual alpha frequency (IAF) also modulated the relationship between article surprisal and the N400, emphasising the importance of individual neural factors for prediction. The present study extends upon existing neurocognitive models of language and prediction more generally, by illuminating the flexible and subject-specific nature of predictive processing.
Drivers of customers' efforts to cope with wearable device usage problems and the role of demographics in a study in China
Authors: Ren Tianbao , Le Hoang T.P.M. , Park Jungkun
Published: May 2023

Purpose

This study aims to investigate determinants such as performance expectancy (PE), health beliefs (HB), technological compatibility, trust and social influence (SI) of customers' efforts to cope with problems associated with using wearable health technology, thereby determining their use intention of such products. The moderating effect of the demographic variables is also investigated.

Design/methodology/approach

An online survey was used to collect panel data from 285 respondents in China. Structural equation modeling was used to test the hypotheses, and interaction moderation was applied to test the moderating effect of the demographic variables.

Findings

The results show that HB, technological compatibility, trust and SI significantly impact coping efforts associated with usage, which significantly influences intention to use. Only income significantly moderated the effect of coping efforts on the intention to use.

Originality/value

This is the first study combining coping theory and UTAUT to develop a model of drivers that encourages customers to overcome the constraints of using wearable technologies.
Diversity–performance nexus in an emerging economy: an investigation of family and non-family firms
Authors: Islam Md Tariqul , Saha Shrabani , Rahman Mahfuzur
Published: May 2023

Purpose

The empirical study aims to examine the impact of board diversity with respect to gender and nationality on firm performance in an emerging economy. This research further splits the sample into family and non-family domains and investigates the diversity–performance nexus in isolation.

Design/methodology/approach

The sample consists of 183 listed companies in Bangladesh over the period 2007 to 2017. This study employed the generalised method of moments (GMM) technique to address the possible endogeneity issue in the governance–performance connection. To underscore the strength of diversity, three distinctive assessment measures were used: percentage representation of females and foreign directors, the Blau index and the Shannon index.

Findings

The results for the full sample models reveal that board heterogeneity regarding both female and foreign directors positively and significantly influences firm performance as measured by return on assets (ROA). Further to this, female directors in family-owned businesses have a positive association with profitability, whereas foreign nationals demonstrate a significant positive association with performance in non-family firms. Additionally, at least three women directors are needed to make a positive difference in profitability; however, a sole director with foreign nationality is capable of demonstrating a similar impact on performance.

Practical implications

The findings are significant for policymakers and organisations that advocate diversity on corporate boards of directors, and the minimum number of diverse board members needs to be considered depending on the identity to bring about a significant change in organisational outcome. Therefore, the findings of this study may be applied to other emerging economies with similar institutional characteristics.

Originality/value

This study reinforces the existing stock of knowledge on the impact of board diversity on the profitability of firms, especially in the context of an emerging economy – Bangladesh. Irrespective of the given backdrop, this study finds that both gender and nationality diversity in the case of Bangladesh is found to have a positive and significant effect on financial performance with respect to all the diversity metrics, i.e. the proportionate number of female and foreign directors on the boards, the Blau index and the Shannon index.
Bridging the digital divide in Africa via universal service funds: an institutional theory perspective
Authors: Arakpogun Emmanuel Ogiemwonyi , Whalley Jason , Wanjiru Roseline , Elsahn Ziad , Kummitha Rama Krishna Reddy
Published: May 2023

Purpose

The purpose of this paper is to provide evidence-based policy recommendations for improving the implementation of universal service funds (USF) with a view to closing the digital divide in Africa.

Design/methodology/approach

The paper adopts a qualitative approach that draws examples from various African countries supported by 25 interviews from key stakeholders with hands-on experience and roles that shape telecommunications policy in Africa and other developing countries.

Findings

The study's findings point out that institutional voids which characterize several African countries inhibit the effectiveness of USF in African countries. The authors identify several institutional and organisational factors and explain how they negatively affect the performance of USF. The authors find that in order to overcome these obstacles, there is a need for a clear redefinition of Universal Access and Service (UAS) policies, restructuring the governance of USF, encouraging cross-sectoral collaborations, and bottom-up initiatives to bridge the digital divide in African countries.

Originality/value

The paper contributes to the underexplored USF literature by shedding light on the role of institutional factors in determining the success of USF. The paper thus complements and provides a different perspective on promoting digital inclusion in Africa from the viewpoint of institutional voids, bringing new insights into the existing literature on how to deal with an intractable area of UAS policy and the wider digital divide debate in developing countries.
The evolving field of global mobility: responses to global volatility (2013–2022)
Authors: Ridgway Maranda , Langinier Hélène
Published: May 2023

Purpose

A decade has passed since Dabicet al. (2015) published a systematic review of the evolution of the expatriate literature from 1970 to 2012. Moreover, the past five years have been turbulent, with many global crises affecting organizational approaches to the global movement of people, particularly expatriate workers. Thus, this article seeks to understand how global mobility has continued to evolve during such turbulence and propose avenues for future research.

Design/methodology/approach

In this study, the authors undertook a constructive replication (Köhler and Cortina, 2021) of the systematic literature review conducted by Dabicet al. (2015), informed by guidelines offered by Donthuet al. (2021) for the period 2013 to 2022. The authors conducted a performance analysis of 1,517 academic articles about expatriates and broader globally mobile workers. Additionally, the authors analyzed all expatriate-related special issues published in the past decade and provide a narrative review of seminal works from the past five years.

Findings

The expatriation field has grown exponentially; greater attention has been paid to contextualizing research, particularly concerning emerging markets, although the field remains Western-dominant. This analysis stresses the increasingly strategic nature of expatriation at a time when global staffing has become dramatically challenging. Thus, this review highlights the need for more interdisciplinarity at different levels between expatriation and the field of strategy. The authors argue the need for a multifaceted understanding of the expatriation experience.

Originality/value

The authors offer a constructive replication of a bibliometric literature review extended by a narrative analysis to complement a critical perspective on a large set of bibliographic data on the broad subject of expatriation. This addition offers an integrated view of the different themes identified by the bibliometric analysis and paves the way for future replication studies to examine how fields evolve.
Leader–member exchange and innovative work behavior: a 2-1-1 model
Authors: Dar Nasib , Kundi Yasir Mansoor , Soomro Shuaib Ahmed
Published: May 2023

Purpose

This study aims to examine the link between leader–member exchange (LMX) and employee innovative work behavior (IWB) by using employee job crafting as a mediator.

Design/methodology/approach

The study uses multilevel, multisource and multiwave data collected from 284 employees working in the banking sector of Pakistan.

Findings

The study findings suggest a significant positive relationship between (i) LMX and job crafting dimensions and (ii) job crafting dimensions and employee IWB. Job crafting dimensions mediated the impact of LMX on IWB, except for relational crafting, which was not significant. Multilevel analysis demonstrated significant individual-level job crafting and IWB.

Originality/value

This study undertakes a multilevel mediational analysis to examine the relationship between LMX and IWB, which is rarely applied in the existing literature. Moreover, this study contributes to understanding how LMX influences IWB using the conservation of resources theory.
Algorithms for better decision-making: a qualitative study exploring the landscape of robo-advisors in India
Authors: Nain Indu , Rajan Sruthi
Published: May 2023

Purpose

This paper explores the current state of Robo-advisory services in India. This paper further highlights the problems experienced by the service providers in disseminating the innovative business model among the Indians.

Design/methodology/approach

The study adopts a qualitative approach to investigate the industry experts by conducting semi-structured interviews. The data collected were transcripted and further analyzed using the content analysis technique. Finally, the authors utilized categorization and coding techniques to frame broad study themes.

Findings

The study findings reveal that the three pillars of Robo-advisory are ease and convenience, the time factor and transparency in operations. Robo-advisory services are still at a nascent stage in India. Furthermore, keeping the sentiments of Indians in mind, FinTech companies could combine automated Robo-advisory with a human touch of a wealth manager for optimal advisory services.

Research limitations/implications

Since the present study is qualitative, the authors cannot generalize the study results. Future research can focus on empirically proving the constructs of the study using quantitative methods.

Practical implications

Robo-advisors have a well-established market in developed nations but are still nascent in developing countries like India. The current focus of service providers and regulatory authorities must be to increase awareness among investors by educating the investors and building trust.

Originality/value

The present study is the first to qualitatively synthesize the challenges faced by the FinTech service providers in the Indian market.
Barrier function and ultrastructure characteristics of epidermis in patients with primary cutaneous amyloidosis
Authors: Zhang Yuling , Le Ya , Guo Junyi , Wu Fangfang , Li Qing , Lu Ping
Published: May 2023

Previous studies on primary cutaneous amyloidosis (PCA) have mainly focused on exploring genetic mutation and components of amyloid in patients with PCA. However, studies on skin barrier function in PCA patients are scarce. Here, we detected the skin barrier function in PCA patients and healthy people by using noninvasive techniques and characterized ultrastructural features of PCA lesions compared with healthy people using transmission electron microscopy (TEM). The expression of proteins related to skin barrier function was examined by immunohistochemistry staining. A total of 191 patients with clinically diagnosed PCA and 168 healthy individuals were enrolled in the study. Our analysis revealed that all investigated lesion areas displayed higher transepidermal water loss and pH values, and lower Sebum levels and stratum corneum hydration levels in PCA patients compared with the same site area in healthy individuals. The TEM results showed that the intercellular spaces between the basal cells were enlarged and the number of hemidesmosomes decreased in PCA lesions. Immunohistochemical staining showed that the expression of integrin α6 and E‐cadherin in PCA patients was less than that in healthy controls, while no differences in the expression of loricrin and filaggrin were observed. Our study revealed that individuals with PCA displayed skin barrier dysfunction, which may be related to alterations in epidermal ultrastructure and a decrease in the skin barrier‐related protein E‐cadherin. However, the molecular mechanisms underlying skin barrier dysfunction in PCA remain to be elucidated.