bluuebunny/crossref_metadata_2025 huggingface dataset:
The natural history of curve behavior after brace removal in adolescent idiopathic scoliosis: a literature review
Authors: Luhmann Scott , Zaaroor-Regev Daphna , Upasani Vidyadhar V. , Shufflebarger Harry
Published: January 2023

Purpose

Brace treatment is the most common nonoperative treatment to prevent curve progression in adolescent idiopathic scoliosis (AIS). The goal of this review and analysis is to characterize curve behavior after completion of brace treatment and to identify factors that may facilitate the estimation of long-term curve progression.

Method

A review of the English language literature was completed using the MEDLINE (PUBMED) database of publications after 1990 until September 2020. Studies were included if they detailed a minimum of 1 year post-brace removal follow-up of AIS patients. Data retrieved from the articles included Cobb angle measurements of the major curves at “in-brace,” weaning, and follow-up visit(s) for all patients described and for subset populations.

Results

From 75 articles, 18 relevant studies describing a follow-up period of 1–25 years following brace removal were included in the analyses. The reviewed literature demonstrates that curves continue to progress after brace treatment is completed with three main phases of progression: (i) immediate (upon brace removal) where a mean curve progression of 7° occurs; (ii) short term (within five years of brace removal) where a relatively high progression rate is evident (0.8°/year); and (iii) long term (more than five years after brace removal) where the progression rate slows (0.2°/year). The magnitude and rate of curve progression is mainly dependent on the degree of curve at weaning as curves weaned at < 25° progress substantially less than curves weaned at ≥ 25° at 25 years.

Conclusion

Curves continue to progress after brace removal and the rate and magnitude of progression are associated with the curve size at weaning, with larger curves typically exhibiting more rapid and severe progression. This analysis provides physicians and patients the ability to estimate long-term curve size based on the curve size at the time of weaning.

Level of evidence

IV.
A Modified Sliding-Lengthening Approach to Tendon Lengthening with a Locking Mechanism Suture: A Technical Note
Authors: Iwase Dai , Metoki Yukie , Aikawa Jun , Uchida Kentaro , Fukushima Kensuke , Matsuo Takashi , Matsuo Atsushi , Inoue Gen , Takaso Masashi
Published: January 2023

There are various techniques used for tendon lengthening, of which Z-lengthening and sliding-lengthening are the most frequently performed. In patients with cerebral palsy, tendon lengthening may often be necessary at multiple sites. However, they can cause various complications, such as inaccurate extension, overextension, and a lack of tendon continuity. We modified the sliding-lengthening technique with a locking mechanism to address these issues. This technical note aims to describe the surgical technique and pitfalls associated with the modified sliding-lengthening approach and suture locking mechanism. The tendon was exposed and stabilized using sterilized spitz tubes and was then threaded so that each loop length was equivalent to the amount of tendon extension. Symmetrical hemisection of both ends of the tendon was performed, and the tendon was carefully extended to create a tense loop. The modified sliding-lengthening technique with the locking suture mechanism may be an advantageous method that accurately addresses extension volume, prevents hyperextension, and maintains tendon continuity, even when smaller incisions are used.
A pragmatic perspective on AI transparency at workplace
Authors: Al-Sulaiti Ghanim , Sadeghi Mohammad Amin , Chauhan Lokendra , Lucas Ji , Chawla Sanjay , Elmagarmid Ahmed
Published: January 2023

Recently, artificial intelligence (AI) systems have been widely used in different contexts and professions. However, with these systems developing and becoming more complex, they have transformed into black boxes that are difficult to interpret and explain. Therefore, urged by the wide media coverage of negative incidents involving AI, many scholars and practitioners have called for AI systems to be transparent and explainable. In this study, we examine transparency in AI-augmented settings, such as in workplaces, and perform a novel analysis of the different jobs and tasks that can be augmented by AI. Using more than 1000 job descriptions and 20,000 tasks from the O*NET database, we analyze the level of transparency required to augment these tasks by AI. Our findings indicate that the transparency requirements differ depending on the augmentation score and perceived risk category of each task. Furthermore, they suggest that it is important to be pragmatic about transparency, and they support the growing viewpoint regarding the impracticality of the notion of full transparency.
Projection-iterated method for solving numerically the nonlinear mixed integral equation in position and time
Authors: Al Hazmi Sharifah E.
Published: January 2023

In this work, we consider a nonlinear Volterra-Hammerstein integral equation of the second kind (V-HIESK). The existence of a unique solution to the integral equation, under certain conditions, is guaranteed. The projection method was used, as the best numerical method. This method is better than the previous methods in the possibility of obtaining the lowest relative error. The method of obtaining the best approximate solution, through the projection method, depends on presenting three consecutive algorithms and depends mainly on the method of iterative projection (P-IM). In each algorithm, we get the approximate solution and the corresponding relative error. Moreover, we demonstrated that the estimated error of P-IM in the first algorithm is better than that of the successive approximation method (SAM). Some numerical results were calculated, and the error estimate was computed, in each case. Finally, the numerical results have been compared between this method and previous research, and it is clear through the same examples that the relative error of the first algorithm is better than the comparative error in the other methods.
Reason-Based Abortion Bans, Disability Rights, and the Future of Prenatal Genetic Testing
Authors: Roesner Nina , Jamal Leila , Wasserman David , Berkman Benjamin E.
Published: January 2023

Recent advances in prenatal genetic testing have made testing for congenital disorders more accessible, with emerging technologies promising further expansion of available testing options. In particular, non-invasive prenatal testing (“NIPT”) has allowed women to identify more fetal disorders earlier in pregnancy than was possible only a decade ago. In addition to allowing women to prepare for the birth of a child with a disability, prenatal diagnoses give women the ability to terminate a pregnancy to avoid raising a child with a disability, a choice driven by myriad factors.
Impact of phenotypic rapid diagnostic assay on duration of empiric antibiotics for gram-negative bacteremia
Authors: Mohayya Sana M. , Arsalan Mohammad , Narayanan Navaneeth , Patel Purvi , Hong Christin G. , Kirn Thomas J. , Bhatt Pinki J. , Bhowmick Tanaya
Published: January 2023

Objective:

Rapid diagnostic tests (RDTs) are increasingly being implemented as antimicrobial stewardship tools to facilitate antibiotic modification and reduce complications related to their overutilization. We measured the clinical impact of a phenotypic RDT with antimicrobial stewardship (AMS) in the setting of gram-negative bacteremia.

Setting and participants:

In this single-center retrospective cohort study, we evaluated adult patients with gram-negative bacteremia who received at least 72 hours of an antibiotic.

Methods:

The primary outcome was the duration of empiric antibiotic therapy for gram-negative bacteremia. Secondary outcomes included time-to-directed therapy, proportion of modifications, hospital length of stay (LOS), and subsequent infection with a multidrug-resistant organism (MDRO) or C. difficile infection (CDI).

Results:

The duration of empiric antibiotics decreased in the RDT+AMS group (4 days vs 2 days; P < .01). Time to directed therapy decreased from 75.0 to 27.9 hours (P < .01).

Conclusions:

The clinical outcomes of LOS, MDRO, and CDI were reduced. The phenotypic RDT demonstrated an improvement in stewardship measures and clinical outcomes.
Evaluation of stress markers in horses during hippotherapy sessions in comparison to being ridden by beginners
Authors: Potier Julie FN , Louzier Vanessa
Published: January 2023

Hippotherapy has been used for decades and its benefits to human patients have largely been proven, whether being applied to those with physical or mental disabilities. There have been a plethora of animal welfare studies recently, pertaining especially to ridden horses. This study aimed to investigate stress markers in horses during hippotherapy sessions to address the ethical considerations raised by using horses for therapy. A ridden stress ethogram was established and validated specifically for this study via subjective observation and video recording of a ridden session involving intermediate-level riders. The experiment entailed eight healthy horses undergoing two ridden sessions on separate days, one with disabled riders and one with beginners. Several parameters associated with physiological responses to stress were evaluated at rest, such as heart rate, plasma adrenocorticotropic hormone [ACTH], serum and salivary cortisol. These parameters as well as the behavioural stress score from the ethogram scale were measured during both sessions. No significant differences were found between heart rate, plasma ACTH, and stress scores. Serum and salivary cortisol were significantly lower during the hippotherapy session than during the session with beginners. The current study found no evidence of compromised welfare when horses were used as a therapeutic aid during hippotherapy sessions compared to their usual ridden activity. Although these results indicate that hippotherapy may be ethically justified as it benefits humans without causing harm to the horses, the present study was small, and the results should be interpreted with caution.
Rituximab for Pediatric Central Nervous System Inflammatory Disorders in Alberta, Canada
Authors: Pecuh Ihor , Slobodan Jeremy , McCombe Jennifer A. , Morneau-Jacob Francois-Dominique , Smyth Penelope , Wilbur Colin
Published: January 2023

Background:

Early and effective treatment of central nervous system (CNS) inflammatory disorders is vital to reduce neurologic morbidity and improve long-term outcomes in affected children. Rituximab is a B-cell-depleting monoclonal antibody whose off-label use for these disorders is funded in the province of Alberta, Canada, by the Short-Term Exceptional Drug Therapy (STEDT) program. This study describes the use of rituximab for pediatric CNS inflammatory disorders in Alberta.

Methods:

Rituximab applications for CNS inflammatory indications in patients <18 years of age were identified from the STEDT database between January 1, 2012, and December 31, 2019. Patient information was linked to other provincial datasets including the Discharge Abstract Database, Pharmaceutical Information Network, and Provincial Laboratory data. Analysis was descriptive.

Results:

Fifty-one unique rituximab applications were identified, of which 50 were approved. New applications increased from one in 2012 to a high of 12 in 2018. The most common indication was autoimmune encephalitis without a specified antibody (n = 16, 31%). Most children were approved for a two-dose (n = 33, 66%) or four-dose (n = 16, 32%) induction regimen. Physician-reported outcomes were available for 24 patients, of whom 14 (58%) were felt to have fully met outcome targets.

Conclusion:

The use of rituximab for pediatric CNS inflammatory disorders has increased, particularly for the indication of autoimmune encephalitis. This study identified significant heterogeneity in dosing practices and laboratory monitoring. Standardized protocols for the use of rituximab in these disorders and more robust outcome reporting will help better define the safety and efficacy of rituximab in this population
Disk wakes in nonlinear stratification
Authors: Gola Divyanshu , Nidhan S. , Ortiz-Tarin J.L. , Pham H.T. , Sarkar S.
Published: January 2023

Nonlinearity of density stratification modulates buoyancy effects. We report results from a body-inclusive large eddy simulation of a wake in nonlinear stratification, specifically for a circular disk at diameter-based Reynolds number (

${\it Re} $

) of

$5000$

. Five density profiles are considered; the benchmark has linear stratification and the other four have hyperbolic tangent profiles of the same thickness to model a pycnocline. The disk moves inside the central core of the pycnocline in two of those four cases and, in the other two cases with a shifted density profile, the disk moves partially/completely outside the pycnocline. The maximum buoyancy frequency (

$N_{max}$

) for all the profiles is the same. The first part of the study investigates the centred cases. Non-uniform stratification results in increasing wake turbulence relative to the benchmark owing to reduced suppression of turbulence production as well as wave trapping in the pycnocline. Steady lee waves are also quantified to understand the limitations of linear theory. The second part pays attention to the effect of a relative shift between the pycnocline and the disk. The wake defect velocity decays substantially faster in the cases with a shift and the wake has higher turbulence level. The effect of disk location on the Kelvin wake waves (a family of steady waves within the pycnocline) and its modal form is obtained and explained by solving the Taylor–Goldstein equation. The family of unsteady internal gravity waves that are generated by the wake is also studied and the effect of disk shift is quantified.
A peer support dietary change intervention for encouraging adoption and maintenance of the Mediterranean diet in a non-Mediterranean population (TEAM-MED): lessons learned and suggested improvements
Authors: Appleton Katherine M. , McEvoy Claire T. , Lloydwin Christina , Moore Sarah , Salamanca-Gonzalez Patricia , Cupples Margaret E. , Hunter Steven , Kee Frank , McCance David R. , Young Ian S. , McKinley Michelle C. , Woodside Jayne V.
Published: January 2023

Peer support interventions for dietary change may offer cost-effective alternatives to interventions led by health professionals. This process evaluation of a trial to encourage the adoption and maintenance of a Mediterranean diet in a Northern European population at high CVD risk (TEAM-MED) aimed to investigate the feasibility of implementing a group-based peer support intervention for dietary change, positive elements of the intervention and aspects that could be improved. Data on training and support for the peer supporters; intervention fidelity and acceptability; acceptability of data collection processes for the trial and reasons for withdrawal from the trial were considered. Data were collected from observations, questionnaires and interviews, with both peer supporters and trial participants. Peer supporters were recruited and trained to result in successful implementation of the intervention; all intended sessions were run, with the majority of elements included. Peer supporters were complimentary of the training, and positive comments from participants centred around the peer supporters, the intervention materials and the supportive nature of the group sessions. Attendance at the group sessions, however, waned over the intervention, with suggested effects on intervention engagement, enthusiasm and group cohesion. Reduced attendance was reportedly a result of meeting (in)frequency and organisational concerns, but increased social activities and group-based activities may also increase engagement, group cohesion and attendance. The peer support intervention was successfully implemented and tested, but improvements can be suggested and may enhance the successful nature of these types of interventions. Some consideration of personal preferences may also improve outcomes.
Natural Disasters and Corporate Philanthropy: A Double Movement Perspective
Authors: Wan Guoguang , Wang Heli , Geng Xuesong , Huang Kenneth G.
Published: January 2023

This study examines Chinese corporations’ responses to a sudden natural disaster in terms of their philanthropic donations. We apply Polanyi's double movement perspective to argue that rapid market expansion in an emerging economy causes social problems such as large-income disparities and environmental degradation. This calls forth counterforces advocating social responsibility and sustainability. Such countermovements can be strengthened by a major disaster, especially in the domain of corporate philanthropy. The resulting increase in corporate philanthropy persists long after the disaster, especially for those firms with large intra-firm pay disparities, operating in socially contested industries and located in regions with more social foundations. Using the context of China's 2008 Wenchuan earthquake, we find support for these arguments in a sample of Chinese public firms.
Between Arrogance and Despondency: The Shanghai Workers, the Communists, and the Strikes at the Japanese Cotton Mills of 1926
Authors: Yi Shensi
Published: January 2023

In June 1926, Shanghai cotton-mill workers initiated strikes at Japanese-owned factories in Xiaoshadu, protesting the dismissal of workers accused of arson in the workshop. The Chinese Communist Party (CCP) recognized that Chinese workers’ actions should be aligned with their labor movement strategy, and tried to control the scale of the strikes. In August, responding to an incident where Japanese sailors killed a Chinese man, the CCP redirected to launch a large-scale combined strike, catering to Chinese laborers’ demands of Japanese employers, but not accounting for practical market conditions. Drawing on a variety of sources, this article reveals that dissidence in leadership, weaknesses in grassroots organizations, and unrealized alliances made it impossible for the Communists, so-called the vanguard of the working class, to lead the summer strike. Contrarily, the cotton workers coerced the Communists and their controlled labor unions to maximize their benefits. By mid-September, it had failed, causing a serious setback for the CCP. Compared to the CCP's improvisation and confusion, the capitalists took wise countermeasures in the favorable economic climate of 1926, ultimately triumphing over the Communists and workers.
HIV care continuum outcomes among recently diagnosed people with HIV (PWH) in Washington, DC
Authors: Jaurretche Maria , Byrne Morgan , Happ Lindsey Powers , Levy Matt , Horberg Michael , Greenberg Alan , Castel Amanda D. , Monroe Anne K.
Published: January 2023

The Ending the HIV Epidemic initiative aims to decrease new HIV infections and promote test-and-treat strategies. Our aims were to establish a baseline of HIV outcomes among newly diagnosed PWH in Washington, DC (DC), a ‘hotspot’ for the HIV epidemic. We also examined sociodemographic and clinical factors associated with retention in care (RIC), antiretroviral therapy (ART) initiation and viral suppression (VS) among newly diagnosed PWH in the DC Cohort from 2011–2016. Among 455 newly diagnosed participants, 92% were RIC at 12 months, ART was initiated in 65% at 3 months and 91% at 12 months, VS in at least 17% at 3 months and 82% at 12 months and 55% of those with VS at 12 months had sustained VS for an additional 12 months. AIDS diagnosis was associated with RIC (aOR 2.99; 1.13–2.28), ART initiation by 3 months (aOR 2.58; 1.61–4.12) and VS by 12 months (aOR4.87; 1.69–14.03). This analysis contributes to our understanding of the HIV treatment dynamics of persons with recently diagnosed HIV infection in a city with a severe HIV epidemic.
Development and evaluation of the Food Bank Health and Nutrition Assessment
Authors: Nguyen Cassandra J , Kownacki Caitlin , Skaradzinski Veronica , Streitmatter Kaitlyn , Acevedo Stephanie , Ericson Stephen D , Hager Jessica E , McCaffrey Jennifer
Published: January 2023

Objective:

Efforts to improve the nutritional quality and health promotion in the charitable food system have been undertaken. Though methods exist to track these efforts in terms of food banks’ inventory, there are not research-tested tools to assess, monitor and influence policy, systems and environmental (PSE) changes. The study objective was to develop and evaluate a novel assessment tool that could be used to evaluate a food bank’s efforts to improve the promotion of health and nutritious foods.

Design:

The study had five phases: (1) initial development; (2) iterative review and revisions; (3) pilot testing; (4) content validity assessment and (5) inter-rater and test-retest assessment. The Food Bank Health and Nutrition Assessment (FB-HANA) was drafted after reviewing existing policies, nutrition-focused charitable food systems guidance and similar tools for food pantries.

Setting:

Midwestern United States.

Participants:

Eleven food banks.

Results:

Stakeholders and pilot testers provided initial feedback to refine the FB-HANA’s flow, ease of completion and collection of contextual information. External experts rated the FB-HANA and each of the eight objectives as content valid. A set of two assessments completed by twenty-six community-based professionals, employed by Extension and fourteen food bank staff across eleven food banks, supported moderate to excellent inter-rater and test-retest reliability for the FB-HANA overall and each of its objectives.

Conclusions:

Evidence suggests that the FB-HANA can be used by either food bank or community-based professionals, such as Extension staff, to provide a perspective on ways food banks promote health and nutrition through PSE approaches.
Congo Basin Rainforest Is a Net Carbon Source During the Dry Season
Authors: Jiang Xun , Albright Ronald , Creecy Ellen , Li King‐Fai , Liang Mao‐Chang , Newman Sally , Wang Xinyue , Karandana Gamalathge Thishan Dharshana , Yung Yuk L.
Published: January 2023

The Congo basin, with an area of about 3.7 million km2 in the tropical region, contains the second largest rainforest and is considered as a carbon sink for the atmosphere. Here, using Orbiting Carbon Observatory‐2 satellite observations, we show that the atmospheric CO2 over the Congo basin is ∼2 ppm higher than the regional background during June–August, which is primarily due to biomass burning and significantly reduced photosynthetic activities during the dry season. The contribution from the biomass burning is larger than that from the biosphere during June–August. Current budget estimations suggest emissions from biomass burning during the dry season alone account for ∼72% of the Congo basin annual biomass burning emissions and are ∼40% more than the largest terrestrial uptake in the same region during January–March (wet season). Therefore, better seasonal fire management in this region is an important strategy for achieving timely reductions in global carbon emissions as set by international agreements.
Visco‐Collisional Scaling Law of Flow Resistance and Its Application in Debris‐Flow Mobility
Authors: Chen Qian , Song Dongri , Chen Xiaoqing , Zhong Wei
Published: January 2023

Flow resistance against gravity‐driven forces is a key factor controlling debris‐flow mobility, which is an important parameter for hazard risk assessment. In practice, Manning's formula is widely used for debris‐flow mobility analysis. However, this formula depends on the boundary conditions (channel roughness) and neglects the physical mechanisms of debris flow. Based on the systematic analysis of the field observation data of 93 debris‐flow events at Jiangjia Ravine (Yunnan Province, China), this study investigates the dynamic mechanisms and sources of flow resistance of debris flow. As the flows tend to be liquefied, the fluid viscous effect and particle collisions are the main sources of flow resistance. Flow resistance can be described by a visco‐collisional scaling law. Under fixed channel boundary conditions, this law is further incorporated into Manning's formula, bridging the gap between the resistance model based on physical mechanisms and the empirical formula of flow resistance. The modified Manning's coefficient is closely related to flow regimes, giving Manning's coefficient an explicit physical meaning. The modified Manning's coefficient provides a more reasonable basis for the mobility analysis and risk assessment of debris flow.
Peat Decomposition and Erosion Contribute to Pond Deepening in a Temperate Salt Marsh
Authors: Luk Sheron , Eagle Meagan J. , Mariotti Giulio , Gosselin Kelsey , Sanderman Jonathan , Spivak Amanda C.
Published: January 2023

Salt marsh ponds expand and deepen over time, potentially reducing ecosystem carbon storage and resilience. The water filled volumes of ponds represent missing carbon due to prevented soil accumulation and removal by erosion and decomposition. Removal mechanisms have different implications as eroded carbon can be redistributed while decomposition results in loss. We constrained ponding effects on carbon dynamics in a New England marsh and determined whether expansion and deepening impact nearby soils by conducting geochemical characterizations of cores from three ponds and surrounding high marshes and models of wind‐driven erosion. Radioisotope profiles demonstrate that ponds are not depositional environments and that contemporaneous marsh accretion represents prevented accumulation accounting for 32%–42% of the missing carbon. Erosion accounted for 0%–38% and was bracketed using radioisotope inventories and wind‐driven resuspension models. Decomposition, calculated by difference, removes 22%–68%, and when normalized over pond lifespans, produces rates that agree with previous metabolism measurements. Pond surface soils contain new contributions from submerged primary producers and evidence of microbial alteration of underlying peat, as higher levels of detrital biomarkers and thermal stability indices, compared to the marsh. Below pond surface horizons, soil properties and organic matter composition were similar to the marsh, indicating that ponding effects are shallow. Soil bulk density, elemental content, and accretion rates were similar between marsh sites but different from ponds, suggesting that lateral effects are spatially confined. Consequently, ponds negatively impact ecosystem carbon storage but at current densities are not causing pervasive degradation of marshes in this system.
Effects of Agricultural Large‐And Medium‐Sized Reservoirs on Hydrologic Processes in the Arid Shiyang River Basin, Northwest China
Authors: Sang Liyuan , Zhu Guofeng , Xu Yuanxiao , Sun Zhigang , Zhang Zhuanxia , Tong Huali
Published: January 2023

Agricultural large and medium‐sized reservoirs in arid regions increase the water stresses within local hydrologic systems, adding to pressures on aquatic ecosystems and also threatening the sustainability of water resources. Yet, there is limited research concerning how agricultural reservoirs affect the hydrology of inland river basins, which has hampered a comprehensive assessment of sustainable water use in these systems. We explore the use of stable isotopes of water to evaluate the effects of agricultural reservoirs on hydrology and the sustainable use of water in the arid Shiyang River basin. Results show that agricultural large‐ and medium‐sized reservoirs in this arid region alter local isotopic hydrologic patterns increasing water‐body evaporation and enriching the isotopic composition of water near the reservoir. As a result, evaporation losses of reservoir water can be as high as 30.7% in downstream desert reservoirs. Reservoir water also exchanges with surrounding groundwater and contributes 22% to local precipitation due to reservoir evaporation. Detailed studies of individual reservoirs show that the isotopic composition is most enriched at the surface of the reservoir and then gradually depletes toward the bottom. The cumulative effect of multiple large and medium sized reservoirs profoundly alters hydrologic processes in inland river basins, leading to an evaporation‐led water loss in these systems.
Nanomaterial-based microelectrode arrays for in vitro bidirectional brain–computer interfaces: a review
Authors: Liu Yaoyao , Xu Shihong , Yang Yan , Zhang Kui , He Enhui , Liang Wei , Luo Jinping , Wu Yirong , Cai Xinxia
Published: January 2023

A bidirectional in vitro brain–computer interface (BCI) directly connects isolated brain cells with the surrounding environment, reads neural signals and inputs modulatory instructions. As a noninvasive BCI, it has clear advantages in understanding and exploiting advanced brain function due to the simplified structure and high controllability of ex vivo neural networks. However, the core of ex vivo BCIs, microelectrode arrays (MEAs), urgently need improvements in the strength of signal detection, precision of neural modulation and biocompatibility. Notably, nanomaterial-based MEAs cater to all the requirements by converging the multilevel neural signals and simultaneously applying stimuli at an excellent spatiotemporal resolution, as well as supporting long-term cultivation of neurons. This is enabled by the advantageous electrochemical characteristics of nanomaterials, such as their active atomic reactivity and outstanding charge conduction efficiency, improving the performance of MEAs. Here, we review the fabrication of nanomaterial-based MEAs applied to bidirectional in vitro BCIs from an interdisciplinary perspective. We also consider the decoding and coding of neural activity through the interface and highlight the various usages of MEAs coupled with the dissociated neural cultures to benefit future developments of BCIs.
Single-cell RNA-sequencing reveals radiochemotherapy-induced innate immune activation and MHC-II upregulation in cervical cancer
Authors: Liu Chao , Li Xiaohui , Huang Qingyu , Zhang Min , Lei Tianyu , Wang Fuhao , Zou Wenxue , Huang Rui , Hu Xiaoyu , Wang Cong , Zhang Xiaoling , Sun Bing , Xing Ligang , Yue Jinbo , Yu Jinming
Published: January 2023

Radiochemotherapy (RCT) is a powerful treatment for cervical cancer, which affects not only malignant cells but also the immune and stromal compartments of the tumor. Understanding the remodeling of the local ecosystem induced by RCT would provide valuable insights into improving treatment strategies for cervical cancer. In this study, we applied single-cell RNA-sequencing to paired pre- and post-RCT tumor biopsies from patients with cervical cancer and adjacent normal cervical tissues. We found that the residual population of epithelial cells post-RCT showed upregulated expression of MHC class II genes. Moreover, RCT led to the accumulation of monocytic myeloid-derived suppressor cells with increased pro-inflammatory features and CD16+ NK cells with a higher cytotoxic gene expression signature. However, subclusters of T cells showed no significant increase in the expression of cytotoxic features post-RCT. These results reveal the complex responses of the tumor ecosystem to RCT, providing evidence of activation of innate immunity and MHC-II upregulation in cervical cancer.
Stress-related exposures amplify the effects of genetic susceptibility on depression and anxiety
Authors: Wang Rujia ,   Lifelines Cohort Study, Hartman Catharina A. , Snieder Harold
Published: January 2023

It is unclear whether and to what extent stress-related exposures moderate the effects of polygenic risk scores (PRSs) on depression and anxiety. We aimed to examine such moderation effects for a variety of stress-related exposures on depression and anxiety. We included 41,810 participants with both genome-wide genetic data and measurements of depression and anxiety in the Lifelines Cohort Study. Current depression and anxiety were measured by the MINI International Neuropsychiatric Interview. Stress-related exposures included long-term difficulties, stressful life events, reduced social support, childhood trauma, and loneliness, which were measured by self-report questionnaires. PRSs were calculated based on recent large genome-wide association studies for depression and anxiety. We used linear mixed models adjusting for family relationships to estimate the interactions between PRSs and stress-related exposures. Nine of the ten investigated interactions between the five stress-related exposures and the two PRSs for depression and anxiety were significant (Ps < 0.001). Reduced social support, and higher exposure to long-term difficulties, stressful life events, and loneliness amplified the genetic effects on both depression and anxiety. As for childhood trauma exposure, its interaction with the PRS was significant for depression (P = 1.78 × 10–05) but not for anxiety (P = 0.32). Higher levels of stress-related exposures significantly amplify the effects of genetic susceptibility on depression and anxiety. With a large sample size and a comprehensive set of stress-related exposures, our study provides powerful evidence on the presence of polygenic risk-by-environment interactions in relation to depression and anxiety.
Dental manifestations and treatment of hypophosphatemic rickets: A case report and review of literature
Authors: Jin Xinyang , Xu Yuedan , Liu Wei , Shi Zhiwei , Sun Yi , Pan Xinni , Zhang Ling , Fu Baiping
Published: January 2023

Background

The treatment and management of patients suffering from hypophosphatemic rickets (HR) remain a major challenge for dental practitioners and affected patients.

Objectives

To report a case of HR presenting with specific dental findings and to review the dental manifestations and treatment of HR patients.

Methods

Case: A 32-year-old male presented with multiple dental abscesses and short stature. A thorough history was taken followed by clinical oral examination, and relevant radiological investigation was done. Literature research: In 2020, electronic literature searches were carried out in PubMed and complemented by a careful assessment of the reference lists of the identified relevant papers. Articles and reports fulfilled the inclusion criteria: indexed reviews, case series and case reports in English and restricted to human studies were considered.

Results

The intraoral examination revealed multiple dental abscesses and general periodontal disease; the radiographic examination showed poorly defined lamina dura, large pulp chambers and periapical lesions. Based on the contents of the 43 articles identified in the search, the current knowledge of dental manifestations, treatment and management of HR was summarized.

Conclusions

As HR is a multisystem disease, multidisciplinary care is needed. By summarizing current evidences, we proposed an evidence-based dental management and provided recommendations on diagnosis and treatment of the disease.

It is of profound clinical significance to acquire knowledge of the dental manifestations and provide optimal treatment options for patients.
Prognostic impact of extracranial disease control in HER2+ breast cancer-related brain metastases
Authors: Bottosso Michele , Griguolo Gaia , Sinoquet Léa , Guarascio Maria Cristina , Aldegheri Vittoria , Miglietta Federica , Vernaci Grazia , Barbieri Caterina , Girardi Fabio , Jacot William , Guarneri Valentina , Darlix Amélie , Dieci Maria Vittoria
Published: January 2023

Background

Brain metastases (BM) are common among HER2+ breast cancer (BC) and prognostic stratification is crucial for optimal management. BC-GPA score and subsequent refinements (modified-GPA, updated-GPA) recapitulate prognostic factors. Since none of these indexes includes extracranial disease control, we evaluated its prognostic value in HER2+ BCBM.

Methods

Patients diagnosed with HER2+ BCBM at Istituto Oncologico Veneto-Padova (2002–2021) and Montpellier Cancer Institute (2001–2015) were included as exploratory and validation cohorts, respectively. Extracranial disease control at BM diagnosis (no disease/stable disease/response vs. progressive disease) was evaluated.

Results

In the exploratory cohort of 113 patients (median OS 12.2 months), extracranial control (n = 65, 57.5%) was significantly associated with better OS at univariate (median OS 17.7 vs. 8.7 months, p = 0.005) and multivariate analysis after adjustment for BC-GPA (HR 0.61, 95% CI 0.39–0.94), modified-GPA (HR 0.64, 95% CI 0.42–0.98) and updated-GPA (HR 0.63, 95% CI 0.41–0.98). The prognostic impact of extracranial disease control (n = 66, 56.4%) was then confirmed in the validation cohort (n = 117) at univariate (median OS 20.2 vs. 9.1 months, p < 0.001) and multivariate analysis adjusting for BC-GPA (HR 0.41, 95% CI 0.27–0.61), modified-GPA (HR 0.44, 95% CI 0.29–0.67) and updated-GPA (HR 0.42, 95% CI 0.28–0.63).

Conclusions

Extracranial disease control provides independent prognostic information in HER2+ BCBM beyond commonly used prognostic scores.
MmCMS: mouse models’ consensus molecular subtypes of colorectal cancer
Authors: Amirkhah Raheleh , Gilroy Kathryn , Malla Sudhir B. , Lannagan Tamsin R. M. , Byrne Ryan M. , Fisher Natalie C. , Corry Shania M. , Mohamed Noha-Ehssan , Naderi-Meshkin Hojjat , Mills Megan L. , Campbell Andrew D. , Ridgway Rachel A. , Ahmaderaghi Baharak , Murray Richard , Llergo Antoni Berenguer , Sanz-Pamplona Rebeca , Villanueva Alberto , Batlle Eduard , Salazar Ramon , Lawler Mark , Sansom Owen J. , Dunne Philip D.
Published: January 2023

Background

Colorectal cancer (CRC) primary tumours are molecularly classified into four consensus molecular subtypes (CMS1–4). Genetically engineered mouse models aim to faithfully mimic the complexity of human cancers and, when appropriately aligned, represent ideal pre-clinical systems to test new drug treatments. Despite its importance, dual-species classification has been limited by the lack of a reliable approach. Here we utilise, develop and test a set of options for human-to-mouse CMS classifications of CRC tissue.

Methods

Using transcriptional data from established collections of CRC tumours, including human (TCGA cohort; n = 577) and mouse (n = 57 across n = 8 genotypes) tumours with combinations of random forest and nearest template prediction algorithms, alongside gene ontology collections, we comprehensively assess the performance of a suite of new dual-species classifiers.

Results

We developed three approaches: MmCMS-A; a gene-level classifier, MmCMS-B; an ontology-level approach and MmCMS-C; a combined pathway system encompassing multiple biological and histological signalling cascades. Although all options could identify tumours associated with stromal-rich CMS4-like biology, MmCMS-A was unable to accurately classify the biology underpinning epithelial-like subtypes (CMS2/3) in mouse tumours.

Conclusions

When applying human-based transcriptional classifiers to mouse tumour data, a pathway-level classifier, rather than an individual gene-level system, is optimal. Our R package enables researchers to select suitable mouse models of human CRC subtype for their experimental testing.
The interaction of β-arrestin1 with talin1 driven by endothelin A receptor as a feature of α5β1 integrin activation in high-grade serous ovarian cancer
Authors: Masi Ilenia , Ottavi Flavia , Del Rio Danila , Caprara Valentina , Vastarelli Cristina , Giannitelli Sara Maria , Fianco Giulia , Mozetic Pamela , Buttarelli Marianna , Ferrandina Gabriella , Scambia Giovanni , Gallo Daniela , Rainer Alberto , Bagnato Anna , Spadaro Francesca , Rosanò Laura
Published: January 2023

Dissemination of high-grade serous ovarian cancer (HG-SOC) in the omentum and intercalation into a mesothelial cell (MC) monolayer depends on functional α5β1 integrin (Intα5β1) activity. Although the binding of Intα5β1 to fibronectin drives these processes, other molecular mechanisms linked to integrin inside-out signaling might support metastatic dissemination. Here, we report a novel interactive signaling that contributes to Intα5β1 activation and accelerates tumor cells toward invasive disease, involving the protein β-arrestin1 (β-arr1) and the activation of the endothelin A receptor (ETAR) by endothelin-1 (ET-1). As demonstrated in primary HG-SOC cells and SOC cell lines, ET-1 increased Intβ1 and downstream FAK/paxillin activation. Mechanistically, β-arr1 directly interacts with talin1 and Intβ1, promoting talin1 phosphorylation and its recruitment to Intβ1, thus fueling integrin inside-out activation. In 3D spheroids and organotypic models mimicking the omentum, ETAR/β-arr1-driven Intα5β1 signaling promotes the survival of cell clusters, with mesothelium-intercalation capacity and invasive behavior. The treatment with the antagonist of ETAR, Ambrisentan (AMB), and of Intα5β1, ATN161, inhibits ET-1-driven Intα5β1 activity in vitro, and tumor cell adhesion and spreading to intraperitoneal organs and Intβ1 activity in vivo. As a prognostic factor, high EDNRA/ITGB1 expression correlates with poor HG-SOC clinical outcomes. These findings highlight a new role of ETAR/β-arr1 operating an inside-out integrin activation to modulate the metastatic process and suggest that in the new integrin-targeting programs might be considered that ETAR/β-arr1 regulates Intα5β1 functional pathway.
Non-invasive plasma testing for CD274 UTR structural variations by next-generation sequencing in cancer
Authors: Zhang Wenjuan , Cao Jian , Liu Ke , Qu Ziwei , Zheng Ying , Yu Jun , Yu Yishan , Wang Yongsheng , Wu Wendy
Published: January 2023

Immunotherapy is now the main choice of systemic therapy for many cancer patients, while current biomarkers for tumor immunotherapy may be limited by the accessibility of patient tumor tissue or tumor neoplastic content. Rare mutation in the 5’ and 3’-untranslated region (UTR) of CD274 gene (Protein name: PD-L1) has been recently reported in hematologic and solid tumors as a potential biomarker for assessing efficacy during immunotherapy. However, multi-omics analysis for CD274 UTR region, especially circulating tumor DNA (ctDNA), have been little explored in the pan-cancer perspective. We developed a cSMART2.0 technology featured with higher capture efficiency and homogeneity to detect this rare structural variant in 2249 Chinese patients’ cohort with multiple cancers. An incidence of 0.36% was detected in this cohort, consistent with TCGA (The Cancer Genome Atlas), while the prevalence of SV in CD274 UTR region in liver and breast cancer were significantly higher than TCGA. The liquid biopsy result from ctDNA was 100% concordance with gDNA result getting from tumor tissue detection, and further validated by immunohistochemistry (IHC) and multiplex immunofluorescence (mIF) experiments. Patients carrying this SV in CD274 UTR region without driver gene mutation responded to immune checkpoint inhibitors (ICIs). This study proves that rare structural variants in CD274 UTR region exist in various cancer in Chinese population for the first time, which can induce immune escape and be used for prediction of response to ICIs. Liquid biopsy based cSMART 2.0 technology could offer more sensitive and accurate detection to navigate potential ICIs patients and to benefit patients with advanced disease when tissue samples are not available.
Etoposide promotes DNA loop trapping and barrier formation by topoisomerase II
Authors: Le Tung T. , Wu Meiling , Lee Joyce H. , Bhatt Neti , Inman James T. , Berger James M. , Wang Michelle D.
Published: January 2023

Etoposide is a broadly employed chemotherapeutic and eukaryotic topoisomerase II poison that stabilizes cleaved DNA intermediates to promote DNA breakage and cytotoxicity. How etoposide perturbs topoisomerase dynamics is not known. Here we investigated the action of etoposide on yeast topoisomerase II, human topoisomerase IIα and human topoisomerase IIβ using several sensitive single-molecule detection methods. Unexpectedly, we found that etoposide induces topoisomerase to trap DNA loops, compacting DNA and restructuring DNA topology. Loop trapping occurs after ATP hydrolysis but before strand ejection from the enzyme. Although etoposide decreases the innate stability of topoisomerase dimers, it increases the ability of the enzyme to act as a stable roadblock. Interestingly, the three topoisomerases show similar etoposide-mediated resistance to dimer separation and sliding along DNA but different abilities to compact DNA and chirally relax DNA supercoils. These data provide unique mechanistic insights into the functional consequences of etoposide on topoisomerase II dynamics.
A patient-centric modeling framework captures recovery from SARS-CoV-2 infection
Authors: Ruffieux Hélène , Hanson Aimee L. , Lodge Samantha , Lawler Nathan G. , Whiley Luke , Gray Nicola , Nolan Tui H. , Bergamaschi Laura , Mescia Federica , Turner Lorinda , de Sa Aloka , Pelly Victoria S. ,   The Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) BioResource COVID-19 Collaboration, Kotagiri Prasanti , Kingston Nathalie , Bradley John R. , Holmes Elaine , Wist Julien , Nicholson Jeremy K. , Lyons Paul A. , Smith Kenneth G. C. , Richardson Sylvia , Bantug Glenn R. , Hess Christoph
Published: January 2023

The biology driving individual patient responses to severe acute respiratory syndrome coronavirus 2 infection remains ill understood. Here, we developed a patient-centric framework leveraging detailed longitudinal phenotyping data and covering a year after disease onset, from 215 infected individuals with differing disease severities. Our analyses revealed distinct ‘systemic recovery’ profiles, with specific progression and resolution of the inflammatory, immune cell, metabolic and clinical responses. In particular, we found a strong inter-patient and intra-patient temporal covariation of innate immune cell numbers, kynurenine metabolites and lipid metabolites, which highlighted candidate immunologic and metabolic pathways influencing the restoration of homeostasis, the risk of death and that of long COVID. Based on these data, we identified a composite signature predictive of systemic recovery, using a joint model on cellular and molecular parameters measured soon after disease onset. New predictions can be generated using the online tool http://shiny.mrc-bsu.cam.ac.uk/apps/covid-19-systemic-recovery-prediction-app, designed to test our findings prospectively.
Real-world measurements of ground reaction forces of normal gait of young adults wearing various footwear
Authors: Derlatka Marcin , Parfieniuk Marek
Published: January 2023

For years, researchers have been recognizing patterns in gait for purposes of medical diagnostics, rehabilitation, and biometrics. A method for observing gait is to measure ground reaction forces (GRFs) between the foot and solid plate with tension sensors. The presented dataset consists of 13,702 measurements of bipedal GRFs of one step of normal gait of 324 students wearing shoes of various types. Each measurement includes raw digital signals of two force plates. A signal comprises stance-related samples but also preceding and following ones, in which one can observe noise, interferences, and artifacts caused by imperfections of devices and walkway. Such real-world time series can be used to study methods for detecting foot-strike and foot-off events, and for coping with artifacts. For user convenience, processed data are also available, which describe only the stance phase of gait and form ready-to-use patterns suitable for experiments in GRF-based recognition of persons and footwear, and for generating synthetic GRF waveforms. The dataset is accompanied by Matlab and Python programs for organizing and validating data.