bluuebunny/crossref_metadata_2025 huggingface dataset:
David against Goliath? The rise of coastal states at the Indian Ocean Tuna commission
Authors: Sinan Hussain , Andriamahefazafy Mialy , Robertson Kerrie
Published: December 2022

Tuna regional fisheries management organizations (RFMOs) have long suffered from the domination of distant water fishing nations (DWFNs) in decision-making processes. The Indian Ocean Tuna Commission (IOTC) is no exception. In recent years, coastal states of the Indian Ocean (IO) have tried to change this dynamic - led by countries like the Maldives, Kenya, South Africa, and Australia - to deliver greater benefits to the region, including East Africa. These countries are gathered under the informal group of G16 and have increasingly improved their involvement in the IOTC. Here, we ask how the rise of the G16 benefited coastal States through participation and collective understanding in the Indian Ocean. To do this, we analyzed proposals submitted by the G16 for conservation and management measures and the participant lists of the Commission meetings in the past ten years. Our results show that, individually and collectively, the G16 has played a significant role in shaping the IOTC’s rules. The coastal States have established a good representation, with only a handful of Members absent in some years. Unveiling the efforts of coastal countries is essential to guide further capacity building in the region in terms of negotiations. We also call for international oversight of the actions of DWFNs, such as the EU, whose efforts often differ markedly from their claims of being sustainability champions. The G16’s work is essential to keep the coastal States of the Indian Ocean in the driver’s seat for managing Indian Ocean fisheries to benefit future generations.
Incidence, risk factors and clinical outcomes of septic acute renal injury in cancer patients with sepsis admitted to the ICU: A retrospective study
Authors: Yang Yong , Dong Jun , Chen Xiaojie , Chen Renxiong , Wang Hongzhi
Published: December 2022

Background

The purpose of this study was to clarify the incidence, risk factors, and clinical outcomes of septic acute kidney injury (AKI) in cancer patients with sepsis admitted to the intensive care unit (ICU).

Methods

A total of 356 cancer patients admitted to the ICU due to sepsis from January 2016 to October 2021 were analyzed retrospectively. According to the incidence of septic AKI, all patients were divided into the non-AKI group (n = 279) and the AKI group (n = 77). The clinical data after ICU admission were compared between the above two groups, and the risk factors and the clinical outcomes of septic AKI in the ICU were identified.

Results

The incidence of septic AKI in all patients was 21.6% (77/356). LASSO regression and logistic regression all showed that lactate, sequential organ failure assessment (SOFA) score and septic shock were closely related to the occurrence of septic AKI. In terms of clinical outcomes after ICU admission, the rate of mechanical ventilation (MV) and continuous renal replacement therapy (CRRT), MV time, hospitalization time and 28-day mortality in the ICU were significantly higher in the septic AKI group than in the non-septic AKI group. Among the three subgroups of septic AKI (AKI combined with septic shock, septic cardiac dysfunction or acute respiratory failure), the mortality of patients in the subgroup of AKI combined with septic shock was significantly higher than others. CRRT has no significant effect on the short-term outcome of these patients.

Conclusion

Lactate level, SOFA score and septic shock were closely related to the occurrence of septic AKI in the ICU. The clinical outcomes within 28 days after ICU admission of cancer patients with septic AKI were worse than those without septic AKI. The short-term outcome was worse in patients with septic AKI complicated with septic shock. CRRT does not have any significant effect on the short-term prognosis of cancer patients with septic AKI in the ICU.
Applications of artificial intelligence in orthopaedic surgery
Authors: Farhadi Faraz , Barnes Matthew R. , Sugito Harun R. , Sin Jessica M. , Henderson Eric R. , Levy Joshua J.
Published: December 2022

The practice of medicine is rapidly transforming as a result of technological breakthroughs. Artificial intelligence (AI) systems are becoming more and more relevant in medicine and orthopaedic surgery as a result of the nearly exponential growth in computer processing power, cloud based computing, and development, and refining of medical-task specific software algorithms. Because of the extensive role of technologies such as medical imaging that bring high sensitivity, specificity, and positive/negative prognostic value to management of orthopaedic disorders, the field is particularly ripe for the application of machine-based integration of imaging studies, among other applications. Through this review, we seek to promote awareness in the orthopaedics community of the current accomplishments and projected uses of AI and ML as described in the literature. We summarize the current state of the art in the use of ML and AI in five key orthopaedic disciplines: joint reconstruction, spine, orthopaedic oncology, trauma, and sports medicine.
Characterization of plant growth promoting activities of indigenous bacteria of phosphate mine wastes, a first step toward revegetation
Authors: Mghazli Najoua , Bruneel Odile , Zouagui Rahma , Hakkou Rachid , Sbabou Laila
Published: December 2022

Morocco holds the vast majority of the world’s phosphate reserves, but due to the processes involved in extracting and commercializing these reserves, large quantities of de-structured, nutritionally deficient mine phosphate wastes are produced each year. In a semi-arid climate, these wastes severely hamper plant growth and development leading to huge unvegetated areas. Soil indigenous Plant Growth-Promoting Bacteria (PGPB) play a pivotal role in restauration of these phosphate mining wastes by revegetation, by increasing plants development, soil functioning, and nutrient cycling. The development of a vegetative cover above the degraded phosphate wastes, could stabilize and reintegrate these wastes in the surrounding environment. The current study’s objectives were to isolate, characterize, and identify indigenous bacterial strains, and test their PGP activity in vitro and, for the best-performing strains in planta, in order to assess their potential for acting as biofertilizers. A quantitative test for the synthesis of auxin and the production of siderophores as well as a qualitative test for the solubilization of phosphate were performed on all isolated bacterial strains. The production of hydrogen cyanide (HCN), exopolysaccharides (EPS), and enzymes were also examined. Three bacteria, selected among the best PGPB of this study, were tested in planta to determine whether such indigenous bacteria could aid plant growth in this de-structured and nutrient-poor mining soil. Using 16S rRNA gene sequencing, 41 bacterial strains were isolated and 11 genera were identified: Acinetobacter, Agrococcus, Bacillus, Brevibacterium, Microbacterium, Neobacillus, Paenibacillus, Peribacillus, Pseudarthrobacter, Stenotrophomonas, and Raoultella. Among the three best performing bacteria (related to Bacillus paramycoides, Brevibacterium anseongense, and Stenotrophomonas rhizophila), only Stenotrophomonas rhizophila and Brevibacterium anseongense were able to significantly enhance Lupinus albus L. growth. The best inoculation results were obtained using the strain related to Stenotrophomonas rhizophila, improving the plant’s root dry weight and chlorophyll content. This is also, to our knowledge, the first study to show a PGP activity of Brevibacterium anseongense.
Gut bacterial communities and their assembly processing in Cnaphalocrocis medinalis from different geographic sources
Authors: Yang Yajun , Liu Xiaogai , Guo Jiawen , Xu Hongxing , Liu Yinghong , Lu Zhongxian
Published: December 2022

Introduction

The insect gut harbors numerous microorganisms that may have functions in development and reproduction, digestion, immunity and protection, and detoxification. Recently, the influence factors on gut microbiota were evaluated in the rice leaffolderCnaphalocrocis medinalis, a widespread insect pest in paddy fields. However, the relationship between gut microbiota composition and geography is poorly understood inC. medinalis.

Methods

To reveal the patterns ofC. medinalisgut bacterial communities across geographic sources and the ecological processes driving the patterns,C. medinaliswere sampled from six geographic sources in China, Thailand, and Vietnam in 2016, followed by gut bacterial 16S ribosomal RNA gene sequencing.

Results

A total of 22 bacterial phyla, 56 classes, 84 orders, 138 families, 228 genera, and 299 species were generated inC. medinalisfrom six geographic sources. All alpha diversity indices differed among the samples from different geographic sources. Analysis of similarity (ANOSIM) and permutational multivariate analysis of variance (PERMANOVA) both revealed significant differences in the gut microbiota ofC. medinalisfrom six geographic sources. A total of 94 different taxa were screened as indicators for the gut microbiota ofC. medinalisfrom six geographic sources by linear discriminant analysis effect size (LEfSe). The gene ontology (GO) pathways of the gut microbiota inC. medinalisdiffered among geographic sources. In total, the bacterial communities within geographic sources were mainly determined by stochastic processes, and those between geographic sources were mainly determined by deterministic processes.

Discussion

This study elucidates that geography plays a crucial role in shaping the gut microbiota ofC. medinalis. Thus, it enriches our knowledge of gut bacteria inC. medinalisand sheds light on the mechanisms underlyingC. medinalisgut microbial shifts across geography.
Tissue specific signature of HHV-6 infection in ME/CFS
Authors: Kasimir Francesca , Toomey Danny , Liu Zheng , Kaiping Agnes C. , Ariza Maria Eugenia , Prusty Bhupesh K.
Published: December 2022

First exposure to various human herpesviruses (HHVs) including HHV-6, HCMV and EBV does not cause a life-threatening disease. In fact, most individuals are frequently unaware of their first exposure to such pathogens. These herpesviruses acquire lifelong latency in the human body where they show minimal genomic activity required for their survival. We hypothesized that it is not the latency itself but a timely, regionally restricted viral reactivation in a sub-set of host cells that plays a key role in disease development. HHV-6 (HHV-6A and HHV-6B) and HHV-7 are unique HHVs that acquire latency by integration of the viral genome into sub-telomeric region of human chromosomes. HHV-6 reactivation has been linked to Alzheimer’s Disease, Chronic Fatigue Syndrome, and many other diseases. However, lack of viral activity in commonly tested biological materials including blood or serum strongly suggests tissue specific localization of active HHV-6 genome. Here in this paper, we attempted to analyze active HHV-6 transcripts in postmortem tissue biopsies from a small cohort of ME/CFS patients and matched controls by fluorescencein situhybridization using a probe against HHV-6 microRNA (miRNA), miR-aU14. Our results show abundant viral miRNA in various regions of the human brain and associated neuronal tissues including the spinal cord that is only detected in ME/CFS patients and not in controls. Our findings provide evidence of tissue-specific active HHV-6 and EBV infection in ME/CFS, which along with recent work demonstrating a possible relationship between herpesvirus infection and ME/CFS, provide grounds for renewed discussion on the role of herpesviruses in ME/CFS.
Improvements and new functionalities of UNRES server for coarse-grained modeling of protein structure, dynamics, and interactions
Authors: Ślusarz Rafał , Lubecka Emilia A. , Czaplewski Cezary , Liwo Adam
Published: December 2022

In this paper we report the improvements and extensions of the UNRES server (https://unres-server.chem.ug.edu.pl) for physics-based simulations with the coarse-grained UNRES model of polypeptide chains. The improvements include the replacement of the old code with the recently optimized one and adding the recent scale-consistent variant of the UNRES force field, which performs better in the modeling of proteins with the β and the α+β structures. The scope of applications of the package was extended to data-assisted simulations with restraints from nuclear magnetic resonance (NMR) and chemical crosslink mass-spectroscopy (XL-MS) measurements. NMR restraints can be input in the NMR Exchange Format (NEF), which has become a standard. Ambiguous NMR restraints are handled without expert intervention owing to a specially designed penalty function. The server can be used to run smaller jobs directly or to prepare input data to run larger production jobs by using standalone installations of UNRES.
An update on the use of gamma (multi)sensory stimulation for Alzheimer’s disease treatment
Authors: Manippa Valerio , Palmisano Annalisa , Filardi Marco , Vilella Davide , Nitsche Michael A. , Rivolta Davide , Logroscino Giancarlo
Published: December 2022

Alzheimer’s disease (AD) is characterized by reduced fast brain oscillations in the gamma band (γ, > 30 Hz). Several animal studies show that inducing gamma oscillations through (multi)sensory stimulation at 40 Hz has the potential to impact AD-related cognitive decline and neuropathological processes, including amyloid plaques deposition, neurofibrillary tangles formation, and neuronal and synaptic loss. Therefore Gamma Entrainment Using Sensory stimulation (GENUS) is among the most promising approaches for AD patients’ treatment. This review summarizes the evidence on GENUS effectiveness, from animal models to AD patients. Despite the application on human is in its infancy, the available findings suggest its feasibility for the treatment of AD. We discuss such results in light of parameter improvement and possible underlying mechanisms. We finally emphasize the need for further research for its development as a disease-modifying non-pharmacological intervention.
Protocol to assess rewarding brain stimulation as a learning and memory modulating treatment: Comparison between self-administration and experimenter-administration
Authors: Vila-Solés Laia , García-Brito Soleil , Aldavert-Vera Laura , Kádár Elisabet , Huguet Gemma , Morgado-Bernal Ignacio , Segura-Torres Pilar
Published: December 2022

Intracranial electrical self-stimulation (ICSS) is a useful procedure in animal research. This form of administration ensures that areas of the brain reward system (BRS) are being functionally activated, since the animals must perform an operant response to self-administer an electrical stimulus. Rewarding post-training ICSS of the medial forebrain bundle (MFB), an important system of the BRS, has been shown to consistently improve rats’ acquisition and retention in several learning tasks. In the clinical setting, deep brain stimulation (DBS) of different targets is currently being used to palliate the memory impairment that occurs in some neurodegenerative diseases. However, the stimulation of the MFB has only been used to treat emotional alterations, not memory disorders. Since DBS stimulation treatments in humans are exclusively administered by external sources, studies comparing the efficacy of that form of application to a self-administered stimulation are key to the translationality of ICSS. This protocol compares self-administered (ICSS) and experimenter-administered (EAS) stimulation of the MFB on the spatial Morris Water Maze task (MWM). c-Fos immunohistochemistry procedure was carried out to evaluate neural activation after retention. Results show that the stimulation of the MFB improves the MWM task regardless of the form of administration, although some differences in c-Fos expression were found. Present results suggest that MFB-ICSS is a valid animal model to study the effects of MFB electrical stimulation on memory, which could guide clinical applications of DBS. The present protocol is a useful guide for establishing ICSS behavior in rats, which could be used as a learning and memory-modulating treatment.
Measuring embodiment: A review of methods for prosthetic devices
Authors: Segil Jacob L. , Roldan Leah Marie , Graczyk Emily L.
Published: December 2022

The development of neural interfaces to provide improved control and somatosensory feedback from prosthetic limbs has initiated a new ability to probe the various dimensions of embodiment. Scientists in the field of neuroprosthetics require dependable measures of ownership, body representation, and agency to quantify the sense of embodiment felt by patients for their prosthetic limbs. These measures are critical to perform generalizable experiments and compare the utility of the new technologies being developed. Here, we review outcome measures used in the literature to evaluate the senses of ownership, body-representation, and agency. We categorize these existing measures based on the fundamental psychometric property measured and whether it is a behavioral or physiological measure. We present arguments for the efficacy and pitfalls of each measure to guide better experimental designs and future outcome measure development. The purpose of this review is to aid prosthesis researchers and technology developers in understanding the concept of embodiment and selecting metrics to assess embodiment in their research. Advances in the ability to measure the embodiment of prosthetic devices have far-reaching implications in the improvement of prosthetic limbs as well as promoting a broader understanding of ourselves as embodied agents.
Binge alcohol drinking alters the differential control of cholinergic interneurons over nucleus accumbens D1 and D2 medium spiny neurons
Authors: Kolpakova Jenya , van der Vinne Vincent , Gimenez-Gomez Pablo , Le Timmy , Martin Gilles E.
Published: December 2022

Animals studies support the notion that striatal cholinergic interneurons (ChIs) play a central role in basal ganglia function by regulating associative learning, reward processing, and motor control. In the nucleus accumbens (NAc), a brain region that mediates rewarding properties of substance abuse, acetylcholine regulates glutamatergic, dopaminergic, and GABAergic neurotransmission in naïve mice. However, it is unclear how ChIs orchestrate the control of these neurotransmitters/modulators to determine the synaptic excitability of medium spiny neurons (MSNs), the only projecting neurons that translate accumbens electrical activity into behavior. Also unknown is the impact of binge alcohol drinking on the regulation of dopamine D1- and D2 receptor-expressing MSNs (D1- and D2-MSNs, respectively) by ChIs. To investigate this question, we optogenetically stimulated ChIs while recording evoked and spontaneous excitatory postsynaptic currents (sEPSCs) in nucleus accumbens core D1- and D2-MSN of ChAT.ChR2.eYFPxDrd1.tdtomato mice. In alcohol-naïve mice, we found that stimulating NAc ChIs decreased sEPSCs frequency in both D1- and D2-MSNs, presumably through a presynaptic mechanism. Interestingly, ChI stimulation decreased MSN synaptic excitability through different mechanisms in D1- vs. D2-MSNs. While decrease of ChI-mediated sEPSCs frequency in D1-MSNs was mediated by dopamine, the same effect in D2-MSNs resulted from a direct control of glutamate release by ChIs. Interestingly, after 2 weeks of binge alcohol drinking, optogenetic stimulation of ChIs enhanced glutamate release in D1-MSNs, while its effect on D2-MSNs remained unchanged. Taken together, these data suggest that cholinergic interneurons could be a key target for regulation of NAc circuitry and for alcohol consumption.
A guide for concurrent TMS-fMRI to investigate functional brain networks
Authors: Riddle Justin , Scimeca Jason M. , Pagnotta Mattia F. , Inglis Ben , Sheltraw Daniel , Muse-Fisher Chris , D’Esposito Mark
Published: December 2022

Transcranial Magnetic Stimulation (TMS) allows for the direct activation of neurons in the human neocortex and has proven to be fundamental for causal hypothesis testing in cognitive neuroscience. By administering TMS concurrently with functional Magnetic Resonance Imaging (fMRI), the effect of cortical TMS on activity in distant cortical and subcortical structures can be quantified by varying the levels of TMS output intensity. However, TMS generates significant fluctuations in the fMRI time series, and their complex interaction warrants caution before interpreting findings. We present the methodological challenges of concurrent TMS-fMRI and a guide to minimize induced artifacts in experimental design and post-processing. Our study targeted two frontal-striatal circuits: primary motor cortex (M1) projections to the putamen and lateral prefrontal cortex (PFC) projections to the caudate in healthy human participants. We found that TMS parametrically increased the BOLD signal in the targeted region and subcortical projections as a function of stimulation intensity. Together, this work provides practical steps to overcome common challenges with concurrent TMS-fMRI and demonstrates how TMS-fMRI can be used to investigate functional brain networks.
A coordinate-based meta-analysis of acupuncture for chronic pain: Evidence from fMRI studies
Authors: Yu Zheng , Wang Rong-Rong , Wei Wei , Liu Li-Ying , Wen Chuan-Biao , Yu Shu-Guang , Guo Xiao-Li , Yang Jie
Published: December 2022

Background

Chronic pain (CP) patients tend to represent aberrant functional brain activity. Acupuncture is an effective clinical treatment for CP, and some fMRI studies were conducted to discover the alternation of brain regions after acupuncture therapy for CP. However, the heterogeneity of neuroimaging studies has prevented researchers from systematically generalizing the central mechanisms of acupuncture in the treatment of CP.

Methods

We searched bibliographic databases, including PubMed, EMBASE, PsycINFO, Web of Science Core Collection, ScienceDirect, China Academic Journal Network Publishing Database, etc., and trials registration platforms (From inception to September 1st, 2022). Two independent researchers assessed the study's bias and quality. Furthermore, activation likelihood estimation (ALE) analysis was applied to explore aberrant brain functional activity and acupuncture's central mechanism for CP.

Results

Totally 14 studies with 524 CP patients were included in the study. ALE analysis showed that CP patients presented with decreased ALFF/ReHo in the precuneus, posterior cingulate cortex, right inferior parietal lobule, right superior temporal gyrus, cingulate gyrus, superior frontal gyrus, left medial frontal gyrus including medial prefrontal gurus, left middle frontal gyrus.

Conclusion

This ALE meta-analysis pointed out that acupuncture could modulate the default mode network, the frontoparietal network to treat CP. This provided a systematic summary of the neuroimage biomarker of acupuncture for the treatment of CP.

Systematic review registration

PROSPERO, identifier: CRD42021239633.
Sound localization and auditory selective attention in school-aged children with ADHD
Authors: Fu Tong , Li Bingkun , Yin Weizhen , Huang Shitao , Liu Hongyu , Song Yan , Li Xiaoli , Shang Herui , Zhou Yanling , Cheng Daomeng , Cao Liping , Dang Cai-Ping
Published: December 2022

This study aimed to identify the neurophysiologic bases of auditory attention deficits in children with attention-deficit/hyperactivity disorder (ADHD), focusing on the electroencephalography component of auditory spatial selective attention [the N2 anterior contralateral component (N2ac)]. EEG data were collected from 7- to 11-year-old children with ADHD (n = 54) and age-, sex-, and IQ-matched typically developing (TD) children (n = 61), while they performed an auditory spatial selective task. For behavior, the children with ADHD showed a shorter reaction time (RT) but a higher RT coefficient of variability (RTCV) than TD children. For ERPs, the TD group showed a significant “adult-like” N2ac component; however, the N2ac component was absent in children with ADHD. More importantly, the smaller N2ac component could predict longer RT in both groups, as well as higher severity of inattentive symptoms in children with ADHD. Our results indicated that 7- to 11-year-old TD children have developed an “adult-like” ability to balance auditory target selection and distractor suppression; the absence of N2ac in children with ADHD provided novel evidence supporting their dysfunctional auditory spatial selective attention.
A network meta-analysis on the improvement of cognition in patients with vascular dementia by different acupuncture therapies
Authors: Wen Jiayu , Cao Yu , Chang Surui , Huang Qiaoyi , Zhang Zhen , Wei Wei , Yao Jiuxiu , Pei Hui , Li Hao
Published: December 2022

Introduction

The second most prevalent cause of dementia is vascular dementia (VaD). Furthermore, acupuncture is a relatively safe and effective traditional therapy for individuals with VaD. We performed a network meta-analysis to assess the effectiveness and safety of various acupuncture therapies for VaD based on existing research.

Methods

We searched six electronic databases to screen for randomized controlled trials (RCTs) comparing different acupuncture treatments in VaD patients. The Cochrne tool (Review Manager 5.3) was used to evaluate the risk of bias of the included RCTs. Based on the Grading of Recommendations Assessment, Development and Evaluation framework, we assessed the confidence in the evidence using the Confidence In the results from Network Meta-Analysis approach. We used the frequency approach to perform the network meta-analysis. Data were analyzed using R 4.1.1.

Results

In total, we included 46 eligible studies. The results of the network analysis showed that the combined interventions of moxibustion (MB) with body acupuncture (BA) (MB + BA) and electroacupuncture (EA) with scalp acupuncture (SA) with BA (EA + SA + BA) were more effective in improving cognitive functions and activities of daily living compared with SA or BA alone. However, in the subgroup analysis, EA + SA + BA showed better efficacy in short- and mid-term acupuncture compared with other acupuncture therapies.

Conclusion

Combined acupuncture therapy may be a safe and effective intervention for individuals with VaD, and MB + BA and EA + SA + BA appear to be the most effective interventions. However, because the analysis of this study was based on low-to-moderate evidence, there remains no strong supporting evidence. Thus, high-quality, large-scale, and long-term studies should be conducted in the future to assess the effectiveness and safety of acupuncture in VaD.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier: CRD42022354573.
COnstrained Reference frame diffusion TEnsor Correlation Spectroscopic (CORTECS) MRI: A practical framework for high-resolution diffusion tensor distribution imaging
Authors: Avram Alexandru V. , Saleem Kadharbatcha S. , Basser Peter J.
Published: December 2022

High-resolution imaging studies have consistently shown that in cortical tissue water diffuses preferentially along radial and tangential orientations with respect to the cortical surface, in agreement with histology. These dominant orientations do not change significantly even if the relative contributions from microscopic water pools to the net voxel signal vary across experiments that use different diffusion times, b-values, TEs, and TRs. With this in mind, we propose a practical new framework for imaging non-parametric diffusion tensor distributions (DTDs) by constraining the microscopic diffusion tensors of the DTD to be diagonalized using the same orthonormal reference frame of the mesoscopic voxel. In each voxel, the constrained DTD (cDTD) is completely determined by the correlation spectrum of the microscopic principal diffusivities associated with the axes of the voxel reference frame. Consequently, all cDTDs are inherently limited to the domain of positive definite tensors and can be reconstructed efficiently using Inverse Laplace Transform methods. Moreover, the cDTD reconstruction can be performed using only data acquired efficiently with single diffusion encoding, although it also supports datasets with multiple diffusion encoding. In tissues with a well-defined architecture, such as the cortex, we can further constrain the cDTD to contain only cylindrically symmetric diffusion tensors and measure the 2D correlation spectra of principal diffusivities along the radial and tangential orientation with respect to the cortical surface. To demonstrate this framework, we perform numerical simulations and analyze high-resolution dMRI data from a fixed macaque monkey brain. We estimate 2D cDTDs in the cortex and derive, in each voxel, the marginal distributions of the microscopic principal diffusivities, the corresponding distributions of the microscopic fractional anisotropies and mean diffusivities along with their 2D correlation spectra to quantify the cDTD shape-size characteristics. Signal components corresponding to specific bands in these cDTD-derived spectra show high specificity to cortical laminar structures observed with histology. Our framework drastically simplifies the measurement of non-parametric DTDs in high-resolution datasets with mesoscopic voxel sizes much smaller than the radius of curvature of the underlying anatomy, e.g., cortical surface, and can be applied retrospectively to analyze existing diffusion MRI data from fixed cortical tissues.
Effects of cell size and bicarbonate on single photon response variability in retinal rods
Authors: Geva Polina , Caruso Giovanni , Klaus Colin , Hamm Heidi E. , Gurevich Vsevolod V. , DiBenedetto Emmanuele , Makino Clint L.
Published: December 2022

Accurate photon counting requires that rods generate highly amplified, reproducible single photon responses (SPRs). The SPR is generated within the rod outer segment (ROS), a multilayered structure built from membranous disks that house rhodopsin. Photoisomerization of rhodopsin at the disk rim causes a local depletion of cGMP that closes ion channels in the plasmalemma located nearby with relative rapidity. In contrast, a photoisomerization at the disk center, distant from the plasmalemma, has a delayed impact on the ion channels due to the time required for cGMP redistribution. Radial differences should be greatest in large diameter rods. By affecting membrane guanylate cyclase activity, bicarbonate could impact spatial inhomogeneity in cGMP content. It was previously known that in the absence of bicarbonate, SPRs are larger and faster at the base of a toad ROS (where the ROS attaches to the rest of the cell) than at the distal tip. Given that bicarbonate enters the ROS at the base and diffuses to the tip and that it expedites flash response recovery, there should be an axial concentration gradient for bicarbonate that would accentuate the base-to-tip SPR differences. Seeking to understand how ROS geometry and bicarbonate affect SPR variability, we used mathematical modeling and made electrophysiological recordings of single rods. Modeling predicted and our experiments confirmed minor radial SPR variability in large diameter, salamander rods that was essentially unchanged by bicarbonate. SPRs elicited at the base and tip of salamander rods were similar in the absence of bicarbonate, but when treated with 30 mM bicarbonate, SPRs at the base became slightly faster than those at the tip, verifying the existence of an axial gradient for bicarbonate. The differences were small and unlikely to undermine visual signaling. However, in toad rods with longer ROSs, bicarbonate somehow suppressed the substantial, axial SPR variability that is naturally present in the absence of bicarbonate. Modeling suggested that the axial gradient of bicarbonate might dampen the primary phototransduction cascade at the base of the ROS. This novel effect of bicarbonate solves a mystery as to how toad vision is able to function effectively in extremely dim light.
The role of endogenous opioid neuropeptides in neurostimulation-driven analgesia
Authors: Lubejko Susan T. , Graham Robert D. , Livrizzi Giulia , Schaefer Robert , Banghart Matthew R. , Creed Meaghan C.
Published: December 2022

Due to the prevalence of chronic pain worldwide, there is an urgent need to improve pain management strategies. While opioid drugs have long been used to treat chronic pain, their use is severely limited by adverse effects and abuse liability. Neurostimulation techniques have emerged as a promising option for chronic pain that is refractory to other treatments. While different neurostimulation strategies have been applied to many neural structures implicated in pain processing, there is variability in efficacy between patients, underscoring the need to optimize neurostimulation techniques for use in pain management. This optimization requires a deeper understanding of the mechanisms underlying neurostimulation-induced pain relief. Here, we discuss the most commonly used neurostimulation techniques for treating chronic pain. We present evidence that neurostimulation-induced analgesia is in part driven by the release of endogenous opioids and that this endogenous opioid release is a common endpoint between different methods of neurostimulation. Finally, we introduce technological and clinical innovations that are being explored to optimize neurostimulation techniques for the treatment of pain, including multidisciplinary efforts between neuroscience research and clinical treatment that may refine the efficacy of neurostimulation based on its underlying mechanisms.
Iron status and mental disorders: A Mendelian randomization study
Authors: Qiu Jiaqi , Lian Fuzhi , Fang Xuexian
Published: December 2022

Background

Mental disorders account for an enormous global burden of disease, and has been associated with disturbed iron metabolism in observational studies. However, such associations are inconsistent and may be attributable to confounding from environmental factors. This study uses a two-sample Mendelian randomization (MR) analysis to investigate whether there is any causal effect of systemic iron status on risk of 24 specific mental disorders.

Methods

Genetic variants with concordant relations to 4 biomarkers of iron status (serum iron, ferritin, transferrin saturation, and transferrin) were obtained from a genome-wide association study performed by the Genetics of Iron Status (GIS) consortium. Summary-level data for mental disorders were obtained from the UK Biobank. An inverse-variance weighted (IVW) approach was used for the main analysis, and the simple median, weighted median and MR-Egger methods were used in sensitivity analyses.

Results

Genetically predicted serum iron, ferritin, and transferrin saturation were positively associated with depression and psychogenic disorder, and inversely associated with gender identity disorders. A higher transferrin, indicative of lower iron status, was also associated with increased risk of gender identity disorders and decreased risk of psychogenic disorder. Results were broadly consistent when using multiple sensitivity analyses to account for potential genetic pleiotropy.

Conclusion

Our findings offer a novel insight into mental health, highlighting a detrimental effect of higher iron status on depression and psychogenic disorder as well as a potential protective role on risk of gender identity disorders. Further studies regarding the underlying mechanisms are warranted for updating preventative strategies.
Association between sarcopenia and prognosis of hepatocellular carcinoma: A systematic review and meta-analysis
Authors: Jiang Chuan , Wang Yanyan , Fu Wei , Zhang Guozhuan , Feng Xiaoshan , Wang Xing , Wang Fang , Zhang Le , Deng Yang
Published: December 2022

Background

Sarcopenia, characterized by the loss of muscle mass, strength, and physical ability, occurs with aging and certain chronic illnesses such as chronic liver diseases and cancer. Sarcopenia is common in liver cirrhosis and hepatocellular carcinoma (HCC). Previous reports of association between sarcopenia and prognosis of HCC have been inconsistent. Therefore, the present systematic review and meta-analysis aimed to investigate the impact of sarcopenia on the survival of patients with HCC.

Methods

A systematic literature search was conducted using PubMed, EMBASE, and Web of Science electronic databases from inception to May 1, 2022. We included retrospective or prospective studies investigating the association between sarcopenia and overall survival (OS) and/or progression free survival (PFS) of HCC. We applied the Quality in Prognosis Studies (QUIPS) instrument to evaluate the risk of bias and quality of included studies. The primary and secondary outcomes were the associations of sarcopenia with OS and PFS, respectively, expressed by a pooled hazard ratio (HR) and corresponding 95% confidence interval (CI). Subgroup analysis and sensitivity analysis were performed. We further evaluated the publication bias by the funnel plot and Begg’s test.

Results

A total of 42 studies comprising 8,445 patients were included. The majority of included studies were at an overall low risk of bias. The pooled prevalence of sarcopenia was 39% (95% CI: 33–45%) (n = 8,203). Sarcopenia was associated with an increased risk of shorter OS, with a pooled adjusted HR of 1.84 (95% CI: 1.62–2.09). An independent association between sarcopenia and reduced PFS was observed (HR = 1.33, 95% CI: 1.12–1.56).

Conclusion

The prevalence of sarcopenia was approximately 39% among patients with HCC. Sarcopenia was independently associated with reduced OS and PFS in HCC irrespective of treatment modalities. It is imperative that interventions aimed at alleviating sarcopenia and restoring muscle mass be implemented in order to improve the survival of patients with HCC.

Systematic review registration

[https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022337797], identifier [CRD42022337797].
Current status and challenges of immunotherapy in ALK rearranged NSCLC
Authors: Qi Rongbin , Yu Yingying , Shen Mo , Lv Dongqing , He Susu
Published: December 2022

Rearrangements of the anaplastic lymphoma kinase (ALK) gene account for 5-6% in non-small cell lung cancer (NSCLC). ALK rearranged NSCLC is sensitive to ALK tyrosine kinase inhibitors (TKIs) but prone to drug resistance. Meanwhile, ALK rearranged NSCLC has poor response to single immunotherapy. Here we mainly describe the immune escape mechanisms of ALK mutated NSCLC and the role of related biomarkers. Additionally, we collate and evaluate preclinical and clinical studies of novel immune combination regimens, and describe the prospects and perspectives for the in vivo application of novel immune technologies in patients with ALK rearranged NSCLC.
Gou Qi Zi inhibits proliferation and induces apoptosis through the PI3K/AKT1 signaling pathway in non-small cell lung cancer
Authors: Zhang Lingling , Gong Yanju , Zhang Lei , Liang Bing , Xu Huan , Hu Wangming , Jin Zhong , Wu Xiao , Chen Xiongbin , Li Min , Shi Liangqin , Shi Yaping , Li Mingjian , Huang Yong , Wang Yong , Yang Lan
Published: December 2022

Background

Gou Qi Zi (Lycium barbarum) is a traditional herbal medicine with antioxidative effects. Although Gou Qi Zi has been used to prevent premature aging and in the treatment of non-small cell lung cancer (NSCLC), its mechanism of action in NSCLC remains unclear. The present study utilized network pharmacology to assess the potential mechanism of action of Gou Qi Zi in the treatment of NSCLC.

Methods

The TCMSP, TCMID, SwissTargetPrediction, DrugBank, DisGeNET, GeneCards, OMIM and TTD databases were searched for the active components of Gou Qi Zi and their potential therapeutic targets in NSCLC. Protein-protein interaction networks were identified and the interactions of target proteins were analyzed. Involved pathways were determined by GO enrichment and KEGG pathway analyses using the Metascape database, and molecular docking technology was used to study the interactions between active compounds and potential targets. These results were verified by cell counting kit-8 assays, BrdU labeling, flow cytometry, immunohistochemistry, western blotting, and qRT-PCR.

Results

Database searches identified 33 active components in Gou Qi Zi, 199 predicted biological targets and 113 NSCLC-related targets. A network of targets of traditional Chinese medicine compounds and potential targets of Gou Qi Zi in NSCLC was constructed. GO enrichment analysis showed that Gou Qi Zi targeting of NSCLC was mainly due to the effect of its associated lipopolysaccharide. KEGG pathway analysis showed that Gou Qi Zi acted mainly through the PI3K/AKT1 signaling pathway in the treatment of NSCLC. Molecular docking experiments showed that the bioactive compounds of Gou Qi Zi could bind to AKT1, C-MYC and TP53. These results were verified by experimental assays.

Conclusion

Gou Qi Zi induces apoptosis and inhibits proliferation of NSCLC in vitro and in vivo by inhibiting the PI3K/AKT1 signaling pathway.
Diagnosis and management of AL amyloidosis due to B-cell non-Hodgkin lymphoma
Authors: Berkowitz Callie , Dittus Christopher
Published: December 2022

Immunoglobulin light chain (AL) amyloidosis may be caused by a B-cell non-Hodgkin lymphoma (NHL) rather than a plasma cell neoplasm in rare cases, which presents unique diagnostic and management considerations. NHL associated with AL will often have an IgM paraprotein; thus, this disease is termed IgM-related AL amyloidosis (IgM AL). The clinical presentation of IgM AL is more likely to involve the lungs, peripheral nerves, and soft tissue; cardiac involvement is less common. Patients with IgM AL amyloidosis should undergo a lymphoma-directed work-up including evaluation for nodal and extranodal disease. Additionally, patients with an IgM paraproteinemia should be screened for AL amyloidosis through history and physical examination. Treatment regimens active against underlying lymphoma, rather than plasma cell-directed regimens, are recommended. Historical response rates in IgM AL have been poor; prospective studies of novel antineoplastic regimens may improve treatment outcomes.
Pediatric radius torus fractures in x-rays—how computer vision could render lateral projections obsolete
Authors: Janisch Michael , Apfaltrer Georg , Hržić Franko , Castellani Christoph , Mittl Barbara , Singer Georg , Lindbichler Franz , Pilhatsch Alexander , Sorantin Erich , Tschauner Sebastian
Published: December 2022

It is an indisputable dogma in extremity radiography to acquire x-ray studies in at least two complementary projections, which is also true for distal radius fractures in children. However, there is cautious hope that computer vision could enable breaking with this tradition in minor injuries, clinically lacking malalignment. We trained three different state-of-the-art convolutional neural networks (CNNs) on a dataset of 2,474 images: 1,237 images were posteroanterior (PA) pediatric wrist radiographs containing isolated distal radius torus fractures, and 1,237 images were normal controls without fractures. The task was to classify images into fractured and non-fractured. In total, 200 previously unseen images (100 per class) served as test set. CNN predictions reached area under the curves (AUCs) up to 98% [95% confidence interval (CI) 96.6%–99.5%], consistently exceeding human expert ratings (mean AUC 93.5%, 95% CI 89.9%–97.2%). Following training on larger data sets CNNs might be able to effectively rule out the presence of a distal radius fracture, enabling to consider foregoing the yet inevitable lateral projection in children. Built into the radiography workflow, such an algorithm could contribute to radiation hygiene and patient comfort.
Biomechanics of the lead straight punch of different level boxers
Authors: Liu Yang , Zhu Zhiqiang , Chen Xiuxiu , Deng Chengyuan , Ma Xiujie , Zhao Bin
Published: December 2022

We analyze and compare the differences in the biomechanical parameters between the lead straight punch and the index of force development of the lower extremities of boxers of different levels of ability. This can bridge the technical gap and provide insight and information for training strategies and athlete selection. To this end, a synchronized Vicon infrared 3D motion-capture system, two Kistler force platforms, and Kistler 8 target sensors were used for analysis. Sixteen boxers were recruited and sorted into an elite group (height 181.14 ± 3.01 cm, body mass 76.00 ± 10.028 kg) and a junior group (179.67 ± 5.84 cm, body mass 75.47 ± 12.19 kg), and their lead straight punch was then compared and analyzed. Three punch velocity indexes—peak velocity, contact velocity and Punching deceleration rate—six strength indexes—impulse, peak force, relative strength, peak time (frame), rate of force development (RFD), and movement time—and five exertion of both legs indexes— peak force, peak force/body mass, peak time, RFD index, and RFD/body mass index—were selected for analysis. Significant differences in the peak punch velocity and contact velocity were found between the two groups (7.162 ± 0.475 m•s−1vs. 6.317 ± 0.415 m•s−1, Cohen’s d = 1.89, p < 0.01, 5.557 ± 0.606 m•s−1 vs. 4.874 ± 0.385 m•s−1, Cohen’s d = 1.34, p < 0.05). Furthermore, significant differences were noted in the peak force [(1507.99 ± 411) N vs. (1035.45 ± 220) N, Cohen’s d = 1.43, p < 0.01], relative strength [(21.04 ± 5.88) N•kg−1 vs. (15.61 ± 2.53) N•kg−1, Cohen’s d = 1.19, p < 0.05], impulse [(88.61 ± 25.88) N•ms−1 and (60.53 ± 9.03) N•ms−1, Cohen’s d = 1.45, p < 0.05], and RFD [(88.61 ± 25.88) N•ms−1 and (60.53 ± 9.03) N•ms−1, Cohen’s d = 1.45, p < 0.05]. Among the four indexes of the lower extremities from two embedded Kistler force platforms, there were significant differences in the lead leg’s peak force/body mass [(19.68 ± 4.096) N•kg−1vs. (13.320 ± 2.223) N•kg−1, t = 3.902, Cohen’s d = 1.92, p < 0.01], RFD index [(16.90 ± 3.269) N•ms−1vs. (10.28 ± 4.313) N•ms−1, Cohen’s d = 1.72, p < 0.01], and RFD/body mass index [(23.47 ± 4.09%) N•ms−1Kg−1 vs. (15.38 ± 5.65%) N•ms−1Kg−1, Cohen’s d = 1.64, p < 0.01]. There were no significant differences in the four indexes on the rear leg between the two groups (p > 0.05). Based on the disparity in the effect of the lead straight punch and the biomechanical parameters of both lower extremities, the boxers must attach importance to sequential acceleration-braking training to improve the terminal velocity of the hand, and thus improve the contact velocity. Furthermore, it is advised that coaches and practitioners carefully consider increasing start-up strength training of the lead leg and attempt to improve the peak velocity of the lead straight punch. In addition, these biomechanical parameters can be used as criteria for the selection of boxers.