bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of local injection of tranexamic acid into peri-articular tissue versus drain clamping in total knee arthroplasty: a randomized controlled trial
Authors: Hishimura Ryosuke , Onodera Tomohiro , Ohkoshi Yasumitsu , Okada Kazufumi , Matsuoka Masatake , Matsubara Shinji , Iwasaki Koji , Kondo Eiji , Iwasaki Norimasa
Published: February 2022

Background

Tranexamic acid (TXA) is used as a synthetic anti-fibrinolytic agent for total knee arthroplasty (TKA) to reduce postoperative bleeding. Though the effects on bleeding reduction of several methods of administering TXA have been demonstrated, the optimal method remains controversial. Recently, the hemostatic effect of periarticular local injection of TXA during TKA was reported. Although this method can be expected to suppress postoperative bleeding without placing a drain, its hemostatic effect has not yet been assessed in comparison with local injection and other methods of administering TXA. The aim of this randomized, prospective study was to assess the efficacy of local injection of TXA during TKA.

Methods

To confirm the effect of the local injection of TXA, drain clamping was set as the control. The subjects included a prospective series of 109 patients randomly divided into 2 groups: the local injection (group L) and the drain clamping (group D). The main outcome measure was postoperative bleeding. Secondary outcomes included pain, physical measurements, and laboratory findings.

Results

The calculated total blood loss (CTBL) in groups L and D was nearly equal and did not show the non-inferiority of group L to group D (883 ± 248 vs. 841 ± 257 ml, P = .564). Drained blood loss was significantly higher in group L than in group D (395 ± 130 vs 276 ± 78.8 ml, P < .0001). There was no significant difference in hidden blood loss between the groups (488 ± 269 vs 565 ± 261 ml, P = .131). The other laboratory findings and physical measurements were identical between the groups.

Conclusions

Although CTBL in group L did not show non-inferiority to group D, the local injection of TXA was considered to be superior for suppressing bleeding considering the risk of the adverse effects of using a drain.

Trial registration

This was a randomized, prospective study registered with UMIN Clinical Trials Registry (Registration number: UMIN000036146, date of disclosure: 10/3/2019).
Congenital anomalies-associated Riga–Fede disease as an early manifestation of Lesch–Nyhan syndrome: rare entities in the same pediatric patient—a case report
Authors: Eita Aliaa Abdelmoniem Bedeir
Published: February 2022

Background

Riga–Fede disease is a rare begnin disorder of the oral tissues, it can be associated with congenital anomalies and neurological disturbances. Lesch–Nyhan syndrome is a rare X-linked recessive disorder characterized by neurological and behavioral manifestations. A patient can rarely be diagnosed with both diseases in a lifetime. Therefore, reporting manifestations from such disorders is important to avoid misdiagnosis and help in timely intervention.

Case presentation

This case report presents an 8-months-old male infant with traumatic oral ulcers from deciduous teeth. A diagnosis of Riga–Fede disease was made. Teeth grinding was performed and the oral lesions were healed. At the age of 2.5 years, the patient presented with neurological manifestations as well as facial tissue and premature teeth loss from self mutilation. Genetic sequencing revealed a variant of uncertain significance in the Hypoxanthine Phosphoribosyltransferase 1 gene. He was diagnosed with Lesch–Nyhan syndrome. Cleft palate, ventricular septal defect, congenitally undescended testis and ectopic left iliac kidney were also reported. The patient was scheduled on psychiatric treatment and after about six months of follow-up, both the behavioral and neurological symptoms were improved.

Conclusions

Riga–Fede disease can be an early manifestation of Lesch–Nyhan syndrome. To the best of our knowledge, this is the first reported case with the incidence of all the mentioned entities in one pediatric patient.
Efficacy of 3-day low dose quinine plus clindamycin versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Kenyan children (CLINDAQUINE): an open-label randomized trial
Authors: Obonyo Charles O. , Juma Elizabeth A. , Were Vincent O. , Ogutu Bernhards R.
Published: February 2022

Background

The World Health Organization recommends quinine plus clindamycin as first-line treatment of malaria in the first trimester of pregnancy and as a second-line treatment for uncomplicated falciparum malaria when artemisinin-based drug combinations are not available. The efficacy of quinine plus clindamycin was compared with that of artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in children below 5 years of age.

Methods

An open-label, phase 3, randomized trial was conducted in western Kenya. Children aged 6–59 months with uncomplicated falciparum malaria were randomly assigned (1:1) via a computer-generated randomization list to receive 3 days of twice a day treatment with either oral quinine (20 mg/kg/day) plus clindamycin (20 mg/kg/day) or artemether-lumefantrine (artemether 20 mg, lumefantrine 120 mg) as one (for those weighing 5–14 kg) or two (for those weighing 15–24 kg) tablets per dose. The primary outcome was a PCR-corrected rate of adequate clinical and parasitological response (ACPR) on day 28 in the per-protocol population.

Results

Of the 384 children enrolled, 182/192 (94.8%) receiving quinine plus clindamycin and 171/192 (89.1%) receiving artemether-lumefantrine completed the study. The PCR-corrected ACPR rate was 44.0% (80 children) in the quinine plus clindamycin group and 97.1% (166 children) in the artemether-lumefantrine group (treatment difference − 53.1%, 95% CI − 43.5% to − 62.7%). At 72 h after starting treatment, 50.3% (94 children) in the quinine plus clindamycin group were still parasitaemic compared with 0.5% (1 child) in the artemether-lumefantrine group. Three cases of severe malaria were recorded as serious adverse events in the quinine plus clindamycin group.

Conclusions

The study found no evidence to support the use of a 3-day low dose course of quinine plus clindamycin in the treatment of uncomplicated falciparum malaria in children under 5 years of age in Kenya, where artemether-lumefantrine is still effective.

Trial Registration: This trial is registered with the Pan-African Clinical Trials Registry, PACTR20129000419241.
Malaria prevention interventions beyond long-lasting insecticidal nets and indoor residual spraying in low- and middle-income countries: a scoping review
Authors: Nalinya Sarah , Musoke David , Deane Kevin
Published: February 2022

Background

Significant progress in malaria prevention during the past two decades has prompted increasing global dialogue on malaria elimination. Recent reviews on malaria strategies have focused mainly on long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS), with little emphasis on other prevention methods. This article is a scoping review of literature on malaria prevention methods beyond LLINs and IRS in low- and middle-income countries (LMICs).

Methods

This scoping review found articles published between from 1994 to 2020. Studies were obtained from a search of the PubMed, the Cochrane Library and Social Science abstracts. Grey literature and manual search of secondary references was also done. The search strategy included all study designs but limited only to English. Three independent reviewers performed the selection and characterization of articles, and the data collected were synthesized qualitatively.

Results

A total of 10,112 studies were identified among which 31 met the inclusion criteria. The results were grouped by the 3 emerging themes of: housing design; mosquito repellents; and integrated vector control. Housing design strategies included closing eves, screening of houses including windows, doors and ceilings, while mosquito repellents were mainly spatial repellents, use of repellent plants, and use of plant-based oils. Integrated vector control included larvae source management. Evidence consistently shows that improving housing design reduced mosquito entry and malaria prevalence. Spatial repellents also showed promising results in field experiments, while evidence on repellent plants is limited and still emerging. Recent literature shows that IVM has been largely ignored in recent years in many LMICs. Some malaria prevention methods such as spatial repellents and IVM are shown to have the potential to target both indoor and outdoor transmission of malaria, which are both important aspects to consider to achieve malaria elimination in LMICs.

Conclusion

The scoping review shows that other malaria prevention strategies beyond LLINs and IRS have increasingly become important in LMICs. These methods have a significant role in contributing to malaria elimination in endemic countries if they are adequately promoted alongside other conventional approaches.
Association of HNF1A gene variants and haplotypes with metabolic syndrome: a case–control study in the Tunisian population and a meta-analysis
Authors: Dallali Hamza , Hechmi Meriem , Morjane Imane , Elouej Sahar , Jmel Haifa , Ben Halima Yosra , Abid Abdelmajid , Bahlous Afef , Barakat Abdelhamid , Jamoussi Henda , Abdelhak Sonia , Kefi Rym
Published: February 2022

Background

Variants in the Hepatocyte Nuclear Factor 1 Alpha gene (HNF1A) are associated with lipoproteins levels and type 2 diabetes. In this study, we aimed to assess the association ofHNF1Agene and haplotypes with the metabolic syndrome (MetS) and its components through an association study in the Tunisian population as well as by a meta-analysis.

Methods

A total of 594 Tunisian individuals were genotyped for three variants (rs1169288, rs2464196 and rs735396) located inHNF1Agene using KASPar technology. Statistical analyses were performed with R software. The association was furthermore evaluated through a meta-analysis of our results with those obtained in a Moroccan population.

Results

Our results showed no association betweenHNF1Avariants and MetS in the Tunisian population. However, a significant association was observed between the variant rs735396 and a higher waist circumference. The stratified analysis according to the sex highlighted a significant association between the variant rs1169288 and high cholesterol levels only in women. Similarly, Haplotype analysis showed an association between theHNF1Aminor haplotype and high total cholesterol mainly in women. Finally, our meta-analysis showed no association betweenHNF1Avariants and MetS.

Conclusions

Our findings exclude the involvement of the threeHNF1Avariants rs1169288, rs2464196 and rs735396 in the susceptibility to MetS in our studied Tunisian population but emphasize the role of these variants in the cholesterol homeostasis with sex-specific differences, which may serve to rise clinical consideration to early statin therapy in women carrying these genetic variants.
Mesenchymal stem cells combined with autocrosslinked hyaluronic acid improve mouse ovarian function by activating the PI3K-AKT pathway in a paracrine manner
Authors: Jiao Wenlin , Mi Xin , Yang Yajuan , Liu Ran , Liu Qiang , Yan Tao , Chen Zi-Jiang , Qin Yingying , Zhao Shidou
Published: February 2022

Background

Declining ovarian function in advance-aged women and in premature ovarian insufficiency (POI) patients seriously affects quality of life, and there is currently no effective treatment to rescue ovarian function in clinic. Stem cell transplantation is a promising therapeutic strategy for ovarian aging, but its clinical application is limited due to the low efficiency and unclear mechanism. Here, a novel combination of umbilical cord-mesenchymal stem cells (UC-MSCs) and autocrosslinked hyaluronic acid (HA) gel is explored to rescue ovarian reserve and fecundity in POI and naturally aging mice.

Methods

To investigate HA prolonged the survival after UC-MSCs transplantation, PCR and immunofluorescence were performed to track the cells on day 1, 3, 7 and 14 after transplantation. The effects of HA on UC-MSCs were analyzed by CCK8 assay, RNA-sequencing and 440 cytokine array. In vivo experiments were conducted to evaluate the therapeutic effects of UC-MSCs combined with HA transplantation in 4-vinylcyclohexene diepoxide (VCD)-induced POI mice and naturally aging mice model. Ovarian function was analyzed by ovarian morphology, follicle counts, estrous cycle, hormone levels and fertility ability. To investigate the mechanisms of stem cell therapy, conditioned medium was collected from UC-MSCs and fibroblast. Both in vitro ovarian culture model and 440 cytokine array were applied to assess the paracrine effect and determine the underlying mechanism. Hepatocyte growth factor (HGF) was identified as an effective factor and verified by HGF cytokine/neutralization antibody supplementation into ovarian culture system.

Results

HA not only prolongs the retention of UC-MSCs in the ovary, but also boosts their secretory function, and UC-MSCs promote follicular survival by activating the PI3K-AKT pathway through a paracrine mechanism both in vitro and in vivo. More importantly, HGF is identified as the key functional cytokine secreted by MSCs.

Conclusions

The results show that HA is an excellent cell scaffold to improve the treatment efficiency of UC-MSCs for ovarian aging under both physiological and pathological conditions, and the therapeutic mechanism is through activation of the PI3K-AKT pathway via HGF. These findings will facilitate the clinical application of MSCs transplantation for ovarian disorders.
Path classification by stochastic linear recurrent neural networks
Authors: Boutaib Youness , Bartolomaeus Wiebke , Nestler Sandra , Rauhut Holger
Published: February 2022

We investigate the functioning of a classifying biological neural network from the perspective of statistical learning theory, modelled, in a simplified setting, as a continuous-time stochastic recurrent neural network (RNN) with the identity activation function. In the purely stochastic (robust) regime, we give a generalisation error bound that holds with high probability, thus showing that the empirical risk minimiser is the best-in-class hypothesis. We show that RNNs retain a partial signature of the paths they are fed as the unique information exploited for training and classification tasks. We argue that these RNNs are easy to train and robust and support these observations with numerical experiments on both synthetic and real data. We also show a trade-off phenomenon between accuracy and robustness.
Schizophyllum commune-derived β-glucan improves intestinal health demonstrating protective effects against constipation and common metabolic disorders
Authors: Vu Vuong , Muthuramalingam Karthika , Singh Vineet , Choi Changmin , Kim Young Mee , Unno Tatsuya , Cho Moonjae
Published: February 2022

It has been proven that β-glucan produced by Schizophyllum commune has beneficial effects on obesity, obesity-associated constipation, and colitis conditions; however, the protective effect of the compound on host at basal state is yet to be investigated. C57BL/6 J mice were fed with a normal diet (ND), normal diet supplemented with 3 g/kg (BG_low), and 5 g/kg (BG_high) of β-glucan (BG) for 12 weeks. Body weight, food and water intake and fecal status were monitored weekly. Intestine was stained by Periodic acid–Schiff (PAS) and Alcian Blue to evaluate the mucin layer thickness and goblet cell population. Morphological changes in internal organs and intestinal motility were also assessed, while serum biomarkers for liver injury and glucose level were analyzed. On the other hand, fecal microbiota and associated metabolic activities were also investigated. β-glucan bulked feces, decreased fecal moisture, and proliferated goblet cells resulted in a thickened lubricating mucin layer; however, the intestinal transit rate did not increase. The abundance of beneficial bacteria was increased while the harmful strains was decreased in a dose-dependent manner by the effect of β-glucan. Specific short chain fatty acid (SCFA)-producing strains, such as Roseburia, Ruminococcus, and Bifidobacteria, were selectively increased by β-glucan. In addition, consumption of β-glucan lowered level of obesity-associated biomarkers. Schizophyllum commune β-glucan showed an insignificant change in transit rate in healthy conditions when compared with obesity, despite similar effects on increasing mucus production and bulked feces. Nonetheless, the outcomes proposed protective effects against obesity, diabetes, inflammatory bowel diseases (IBD), and constipation, in which the modification of the gut microbiota by β-glucan is the largest contributor.
The transfer of heritage modelling from research to practice
Authors: Richards Jenny , Brimblecombe Peter
Published: February 2022

Heritage science is an inherently practice-oriented field that aims to support our understanding, and conservation, of heritage. Research is commonly undertaken using laboratory or field-based methodologies, but given the ethical and scale constraints, over time and space, of these approaches, process-based models should provide a tool for exploring practical solutions. Unlike other fields, such as climate science and ecology, there appears limited engagement with modelling within heritage science. The characteristics and use of processed-based models published in the field is examined to explore tensions in using models to transfer understanding between research and practice. By examining models that investigate interactions between heritage materials and environment, we find that, at best, model outputs may be used by other researchers or occasionally by heritage institutions; or more commonly, the model’s existence is used as a justification of research, yet without meaningful engagement within either the academic and heritage practitioner communities. Some models are unlikely to be used in practice as they have been developed at spatial or temporal scales incompatible with being truly applicable to objects or sites, or can seem to advance theory without engaging with practice. The uptake of models by researchers who rerun or change the code is rare. Models that seem to gain substantial use appear to benefit from graphical user interfaces that make them easy to run. Evidence of models in solving real-world conservation problems is hard to find. This may arise because practical applications are rarely reported in academic journal literature and open access publications. There is some evidence they are revealed in conferences and possibly internal heritage organisation reports, but this gray literature doesn’t readily feedback into the development and refinement of existing models. It is likely the use of models would increase if mechanisms were available to support the development of user interfaces, training workshops and the ability of practical use cases to be fed back to the modelling community.
An open-label prospective pilot trial of nucleus accumbens deep brain stimulation for children with autism spectrum disorder and severe, refractory self-injurious behavior: study protocol
Authors: Yan Han , Siegel Lauren , Breitbart Sara , Gorodetsky Carolina , Fasano Alfonso , Rahim Aliya , Loh Alvin , Kulkarni Abhaya V. , Ibrahim George M.
Published: February 2022

Background

Children and youth with autism spectrum disorder (ASD) may manifest self-injurious behaviors (SIB) that may become severe and refractory with limited pharmacologic or behavioral treatment options. Here, we present the protocol of a prospective, mixed-methods study to assess the safety and efficacy of deep brain stimulation (DBS) of the nucleus accumbens (NAcc) for children and youth with ASD and severe, refractory SIB.

Methods

This is a prospective, single-center, single-cohort, open-label, non-randomized pilot trial of 6 patients. Participants will be recruited through specialized behavioral clinics with persistent severe and refractory SIB following standard and intensive interventions. Following NAcc-DBS, participants will be enrolled in the study for 12 months. The primary objectives of the study are safety and feasibility, assessed by rate of recruitment and identification of factors impacting adherence to follow-up and study protocol. Potential treatment efficacy will be assessed by changes in the Children’s Yale-Brown Obsessive-Compulsive Scale in ASD (CYBOCS-ASD), the Behavior Problems Index (BPI), the Inventory of Statements about Self-Injury (ISAS) and the Repetitive Behavior Scale-Revised (RBS-R) questionnaires. Additional clinical outcomes will be assessed, including measures of participant and caregiver quality of life, actigraph measurements, and positron emission tomography (PET) changes following DBS.

Discussion

This study will be the first to evaluate the effect of DBS of the NAcc on a pediatric population in a controlled, prospective trial. Secondary outcomes will improve the understanding of behavioral, neuro-imaging, and electrophysiologic changes in children with ASD and SIB treated with DBS. This trial will provide an estimated effect size of NAcc-DBS for severe refractory SIB in children with ASD in preparation for future comparative trials.

Trial registration

Registration on ClinicalTrials.gov was completed on 12 June 2019 with the Identifier: NCT03982888.
Co-creating with patients an impact framework across the medicine’s life cycle: a qualitative study exploring patients’ experiences of involvement in and perceptions of impact measures
Authors: Gorbenko Oleks , Cavillon Pascale , Giles Rachel H. , Kolarova Teodora , Marks Muriël , Cardone Antonella , Bagga Sandeep , Nolan Claire
Published: February 2022

Background

The biopharmaceutical industry is challenged with efficiently delivering medicines that patients truly value. This can be addressed by engaging patients and caregivers throughout a medicine’s life cycle, ensuring that products meet the needs and expectations of those who take them. While isolated best practice examples of patient engagement exist, they remain relatively ad hoc and not fully embedded within Research & Development (R&D) practices. To encourage more patient engagement, the ‘impact’ of patient engagement projects (PEP) must be objectively measured and demonstrated. Some frameworks have been proposed; however, there is no evidence of widespread adoption, nor have patients’ perspectives been robustly explored. The objective of this qualitative study was therefore to understand patients’ perspectives of impact measurement that can be systematically applied within a biopharmaceutical company.

Methods

Semi-structured interviews were conducted with 13 patient organisation (PO) representatives exploring their experiences of engagement and reflections on 23 candidate patient engagement impact measures categorised into five groups: Medicines R&D Priorities; Clinical Trial Design; Regulatory & Market Access Submissions; Product Support & Information; and Disease Support & Information. Thematic analysis was undertaken and impact measures revised in line with interview participant feedback. Emerging themes and revisions to impact measures were validated at a joint workshop with 4 patient advisors representing 4 POs.

Results

The study revealed that PO representatives feel a deep sense of accomplishment and ownership when collaborating on PEPs with biopharmaceutical companies. They largely conceptualise ‘impact’ as positive, tangible and useful outcomes. The revisions made to the pre-defined patient engagement impact measures fell into three broad categories: (1) a requirement for greater context; (2) capturing the nature of patient influence; and (3) terminology changes. The greatest number of revisions concerned ‘requiring greater context’, for example, including additional descriptions, patient quotes, and satisfaction.

Conclusions

This study sheds light on how patient advocates view ‘impact’. Typically this means delivering ‘value’ important for them. Therefore, the authors of this paper created the term ‘value-impact’ to comprehensively characterise this conceptualisation, and propose a value-impact measurement plan, incorporating longitudinal data. Through this understanding and in light of other recently published work, wide-scale adoption and implementation of the measurement of value-impact across the biopharmaceutical industry can be realised.
Depression and food insecurity among patients with rheumatoid arthritis in NHANES
Authors: Cai Qian , Pesa Jacqueline , Wang Ruibin , Fu Alex Z.
Published: February 2022

Background

Social determinants of health (SDH), including food insecurity, are associated with depression in the general population. This study estimated the prevalence of depression and food insecurity and evaluated the impact of food insecurity and other SDH on depression in adults with rheumatoid arthritis (RA).

Methods

Adults (≥ 18 years) with RA were identified from the 2013–2014 and 2015–2016 National Health and Nutrition Examination Survey (NHANES). Depression was defined as a score of ≥ 5 (mild depression: 5–9; moderate-to-severe depression: 10–27) using the Patient Health Questionnaire-9 (PHQ-9). Food insecurity was assessed with the 18-item US Household Food Security Survey Module. Adults with household-level marginal-to-very-low food security were classified as experiencing food insecurity. The prevalence of depression and food insecurity among participants with RA were estimated. Weighted logistic regression was used to evaluate the association between depression and participants’ characteristics including SDH. Penalized regression was performed to select variables included in the final multivariable logistic regression.

Results

A total of 251 and 276 participants from the 2013–2014 and the 2015–2016 NHANES, respectively, had self-reported RA. The prevalence of depression among these participants was 37.1% in 2013–2014 and 44.1% in 2015–2016. The prevalence of food insecurity was 33.1% in 2013–2014 and 43.0% in 2015–2016. Food insecurity was associated with higher odds of having depression (OR 2.17, 95% CI 1.27, 3.72), and the association varied by depression severity. Compared with participants with full food security, the odds of having depression was particularly pronounced for those with very low food security (OR 2.96, 95% CI 1.48, 5.90) but was not significantly different for those with marginal or low food security. In the multivariable regression, being female, having fair/poor health condition, any physical disability, and ≥ 4 physical limitations were significantly associated with depression.

Conclusions

In adults with self-reported RA, the prevalence of depression and food insecurity remained high from 2013 to 2016. We found that depression was associated with SDH such as food insecurity, although the association was not statistically significant once adjusted for behavioral/lifestyle characteristics. These results warrant further investigation into the relationship between depression and SDH among patients with RA.
Eyes wide open—an atypical presentation of Miller Fisher syndrome (MFS): case report
Authors: Korona Anastasia , Maritsi Despoina , Markante Aikaterini , Stamati Andromachi , Mouskou Stella , Vartzelis George
Published: February 2022

Background

Parinaud’s syndrome, also known as dorsal midbrain syndrome, is characterized by a combination of signs, including upgaze palsy, convergence–retraction nystagmus, eyelid retraction and pupillary dissociation. It is caused by pretectal or tegmental lesions of upper brainstem. Miller Fisher syndrome, characterized by the triad of ataxia, areflexia and ophthalmoplegia, has rarely been reported to present as Parinaud’s syndrome in adults. To our knowledge, this clinical manifestation has not been previously described in children.

Case presentation

A previously healthy 13-year-old girl presented with blurred vision and diplopia, 10 days after a viral infection. Initial examination revealed incomplete Parinaud’s syndrome, while rest of neurological examination was normal. Brain imaging (MRI, MRA) did not reveal any abnormal findings and CSF findings were also normal. During the first days after admission she gradually deteriorated, showing complete external ophthalmoplegia, unsteady gait, and absent deep tendon reflexes of lower limbs with normal muscle power. With the clinical suspicion of Miller Fisher syndrome IVIG was administered, leading to subsequent resolution of her symptoms. AntiGQ1b and antiGD1b antibodies came back positive confirming diagnosis. On 1 month follow-up, neurological examination revealed diplopia in left gaze, and a second dose of IVIG was administered with good response. She remains asymptomatic 1 year from disease onset.

Conclusions

Miller Fisher syndrome can rarely present as Parinaud’s syndrome in adults. Herein we described the first pediatric patient with similar clinical presentation. As the typical semiology of ataxia and areflexia may not be present initially, high index of suspicion is required to recognise and treat those patients promptly. Serological detection of anti-ganglioside antibodies, such as anti-GQ1b and anti-GD1b, may help confirm diagnosis.
Non-rigid registration of medical images based on $$ {S}_2^1\left({\Delta}_{mn}^{(2)}\right) $$ non-tensor product B-spline
Authors: Zheng Qi , Liu Chaoyue , Chang Jincai
Published: February 2022

In this study, a non-tensor product B-spline algorithm is applied to the search space of the registration process, and a new method of image non-rigid registration is proposed. The tensor product B-spline is a function defined in the two directions of x and y, while the non-tensor product B-spline $$ {S}_2^1\left({\Delta}_{mn}^{(2)}\right) $$

S
2
1

Δ
mn

2

is defined in four directions on the 2-type triangulation. For certain problems, using non-tensor product B-splines to describe the non-rigid deformation of an image can more accurately extract the four-directional information of the image, thereby describing the global or local non-rigid deformation of the image in more directions. Indeed, it provides a method to solve the problem of image deformation in multiple directions. In addition, the region of interest of medical images is irregular, and usually no value exists on the boundary triangle. The value of the basis function of the non-tensor product B-spline on the boundary triangle is only 0. The algorithm process is optimized. The algorithm performs completely automatic non-rigid registration of computed tomography and magnetic resonance imaging images of patients. In particular, this study compares the performance of the proposed algorithm with the tensor product B-spline registration algorithm. The results elucidate that the proposed algorithm clearly improves the accuracy.
Genetic and early environmental predictors of adulthood self-reports of trauma
Authors: Peel Alicia J. , Purves Kirstin L. , Baldwin Jessie R. , Breen Gerome , Coleman Jonathan R. I. , Pingault Jean-Baptiste , Skelton Megan , ter Kuile Abigail R. , Danese Andrea , Eley Thalia C.
Published: February 2022

Background

Retrospective self-reports of childhood trauma are associated with a greater risk of psychopathology in adulthood than prospective measures of trauma. Heritable reporter characteristics are anticipated to account for part of this association, whereby genetic predisposition to certain traits influences both the likelihood of self-reporting trauma and of developing psychopathology. However, previous research has not considered how gene–environment correlation influences these associations.

Aims

To investigate reporter characteristics associated with retrospective self-reports of childhood trauma and whether these associations are accounted for by gene–environment correlation.

Method

In 3963 unrelated individuals from the Twins Early Development Study, we tested whether polygenic scores for 21 psychiatric, cognitive, anthropometric and personality traits were associated with retrospectively self-reported childhood emotional and physical abuse. To assess the presence of gene–environment correlation, we investigated whether these associations remained after controlling for composite scores of environmental adversity across development.

Results

Retrospectively self-reported childhood trauma was associated with polygenic scores for autism spectrum disorder (ASD), body mass index (BMI), post-traumatic stress disorder (PTSD) and risky behaviours. When composite scores of environmental adversity were controlled for, only associations with the polygenic scores for ASD and PTSD remained significant.

Conclusions

Genetic predisposition to ASD and PTSD may increase liability to experiencing or interpreting events as traumatic. Associations between genetic predisposition for risky behaviour and BMI with self-reported childhood trauma may reflect gene–environment correlation. Studies of the association between retrospectively self-reported childhood trauma and later-life outcomes should consider that genetically influenced reporter characteristics may confound associations, both directly and through gene–environment correlation.
Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non–Small-Cell Lung Cancer
Authors: Spigel David R. , Faivre-Finn Corinne , Gray Jhanelle E. , Vicente David , Planchard David , Paz-Ares Luis , Vansteenkiste Johan F. , Garassino Marina C. , Hui Rina , Quantin Xavier , Rimner Andreas , Wu Yi-Long , Özgüroğlu Mustafa , Lee Ki H. , Kato Terufumi , de Wit Maike , Kurata Takayasu , Reck Martin , Cho Byoung C. , Senan Suresh , Naidoo Jarushka , Mann Helen , Newton Michael , Thiyagarajah Piruntha , Antonia Scott J.
Published: February 2022

PURPOSE

The phase III PACIFIC trial compared durvalumab with placebo in patients with unresectable, stage III non–small-cell lung cancer and no disease progression after concurrent chemoradiotherapy. Consolidation durvalumab was associated with significant improvements in the primary end points of overall survival (OS; stratified hazard ratio [HR], 0.68; 95% CI, 0.53 to 0.87; P = .00251) and progression-free survival (PFS [blinded independent central review; RECIST v1.1]; stratified HR, 0.52; 95% CI, 0.42 to 0.65; P < .0001), with manageable safety. We report updated, exploratory analyses of survival, approximately 5 years after the last patient was randomly assigned.

METHODS

Patients with WHO performance status 0 or 1 (any tumor programmed cell death-ligand 1 status) were randomly assigned (2:1) to durvalumab (10 mg/kg intravenously; administered once every 2 weeks for 12 months) or placebo, stratified by age, sex, and smoking history. Time-to-event end point analyses were performed using stratified log-rank tests. Medians and landmark survival rates were estimated using the Kaplan-Meier method.

RESULTS

Seven hundred and nine of 713 randomly assigned patients received durvalumab (473 of 476) or placebo (236 of 237). As of January 11, 2021 (median follow-up, 34.2 months [all patients]; 61.6 months [censored patients]), updated OS (stratified HR, 0.72; 95% CI, 0.59 to 0.89; median, 47.5 v 29.1 months) and PFS (stratified HR, 0.55; 95% CI, 0.45 to 0.68; median, 16.9 v 5.6 months) remained consistent with the primary analyses. Estimated 5-year rates (95% CI) for durvalumab and placebo were 42.9% (38.2 to 47.4) versus 33.4% (27.3 to 39.6) for OS and 33.1% (28.0 to 38.2) versus 19.0% (13.6 to 25.2) for PFS.

CONCLUSION

These updated analyses demonstrate robust and sustained OS and durable PFS benefit with durvalumab after chemoradiotherapy. An estimated 42.9% of patients randomly assigned to durvalumab remain alive at 5 years and 33.1% of patients randomly assigned to durvalumab remain alive and free of disease progression, establishing a new benchmark for standard of care in this setting.
Intelligent Vacuum-Assisted Biopsy to Identify Breast Cancer Patients With Pathologic Complete Response (ypT0 and ypN0) After Neoadjuvant Systemic Treatment for Omission of Breast and Axillary Surgery
Authors: Pfob André , Sidey-Gibbons Chris , Rauch Geraldine , Thomas Bettina , Schaefgen Benedikt , Kuemmel Sherko , Reimer Toralf , Hahn Markus , Thill Marc , Blohmer Jens-Uwe , Hackmann John , Malter Wolfram , Bekes Inga , Friedrichs Kay , Wojcinski Sebastian , Joos Sylvie , Paepke Stefan , Degenhardt Tom , Rom Joachim , Rody Achim , van Mackelenbergh Marion , Banys-Paluchowski Maggie , Große Regina , Reinisch Mattea , Karsten Maria , Golatta Michael , Heil Joerg
Published: February 2022

PURPOSE

Neoadjuvant systemic treatment (NST) elicits a pathologic complete response in 40%-70% of women with breast cancer. These patients may not need surgery as all local tumor has already been eradicated by NST. However, nonsurgical approaches, including imaging or vacuum-assisted biopsy (VAB), were not able to accurately identify patients without residual cancer in the breast or axilla. We evaluated the feasibility of a machine learning algorithm (intelligent VAB) to identify exceptional responders to NST.

METHODS

We trained, tested, and validated a machine learning algorithm using patient, imaging, tumor, and VAB variables to detect residual cancer after NST (ypT+ or in situ or ypN+) before surgery. We used data from 318 women with cT1-3, cN0 or +, human epidermal growth factor receptor 2–positive, triple-negative, or high-proliferative Luminal B–like breast cancer who underwent VAB before surgery (ClinicalTrials.gov identifier: NCT02948764 , RESPONDER trial). We used 10-fold cross-validation to train and test the algorithm, which was then externally validated using data of an independent trial (ClinicalTrials.gov identifier: NCT02575612 ). We compared findings with the histopathologic evaluation of the surgical specimen. We considered false-negative rate (FNR) and specificity to be the main outcomes.

RESULTS

In the development set (n = 318) and external validation set (n = 45), the intelligent VAB showed an FNR of 0.0%-5.2%, a specificity of 37.5%-40.0%, and an area under the receiver operating characteristic curve of 0.91-0.92 to detect residual cancer (ypT+ or in situ or ypN+) after NST. Spiegelhalter's Z confirmed a well-calibrated model ( z score –0.746, P = .228). FNR of the intelligent VAB was lower compared with imaging after NST, VAB alone, or combinations of both.

CONCLUSION

An intelligent VAB algorithm can reliably exclude residual cancer after NST. The omission of breast and axillary surgery for these exceptional responders may be evaluated in future trials.
PCP Protein Inversin Regulates Testis Function Through Changes in Cytoskeletal Organization of Actin and Microtubules
Authors: Li Linxi , Gao Sheng , Wang Lingling , Bu Tiao , Chu Jinjin , Lv Lixiu , Tahir Anam , Mao Baiping , Li Huitao , Li Xiaoheng , Wang Yiyan , Wu Xiaolong , Ge Renshan , Cheng C Yan
Published: February 2022

Inversin is an integrated component of the Frizzled (Fzd)/Dishevelled (Dvl)/Diversin planar cell polarity (PCP) complex that is known to work in concert with the Van Gogh-like protein (eg, Vangl2)/Prickle PCP complex to support tissue and organ development including the brain, kidney, pancreas, and others. These PCP protein complexes are also recently shown to confer developing haploid spermatid PCP to support spermatogenesis in adult rat testes. However, with the exception of Dvl3 and Vangl2, other PCP proteins have not been investigated in the testis. Herein, we used the technique of RNA interference (RNAi) to examine the role of inversin (Invs) in Sertoli cell (SC) and testis function by corresponding studies in vitro and in vivo. When inversin was silenced by RNAi using specific small interfering RNA duplexes by transfecting primary cultures of SCs in vitro or testes in vivo, it was shown that inversin knockdown (KD) perturbed the SC tight junction–barrier function in vitro and in vivo using corresponding physiological and integrity assays. More important, inversin exerted its regulatory effects through changes in the organization of the actin and microtubule cytoskeletons, including reducing the ability of their polymerization. These changes, in turn, induced defects in spermatogenesis by loss of spermatid polarity, disruptive distribution of blood-testis barrier–associated proteins at the SC-cell interface, appearance of multinucleated round spermatids, and defects in the release of sperm at spermiation.
How Machines Came to Speak
Authors: Petersen Jennifer
Published: February 2022

In How Machines Came to Speak Jennifer Petersen constructs a genealogy of how legal conceptions of “speech” have transformed over the last century in response to new media technologies. Drawing on media and legal history, Petersen shows that the legal category of speech has varied considerably, evolving from a narrow category of oratory and print publication to a broad, abstract conception encompassing expressive nonverbal actions, algorithms, and data. She examines a series of pivotal US court cases in which new media technologies—such as phonographs, radio, film, and computer code—were integral to this shift. In judicial decisions ranging from the determination that silent films were not a form of speech to the expansion of speech rights to include algorithmic outputs, courts understood speech as mediated through technology. Speech thus became disarticulated from individual speakers. By outlining how legal definitions of speech are indelibly dependent on technology, Petersen demonstrates that future innovations such as artificial intelligence will continue to restructure speech law in ways that threaten to protect corporate and institutional forms of speech over the rights and interests of citizens.
Good night the pleasure was ours
Authors: Grubbs David
Published: February 2022

With Good night the pleasure was ours, David Grubbs melts down and recasts three decades of playing music on tour into a book-length poem, bringing to a close the trilogy that includes Now that the audience is assembled and The Voice in the Headphones. In Good night the pleasure was ours, the world outside the tour filters in with eccentric sparseness. From teenage punk bands to ensembles without fixed membership, and from solo performance to a group augmented by digital avatars, Grubbs presents touring as a series of daily dislocations that provides an education distinctly its own. These musicians’ job is to play that evening’s gig—whether to enthusiastic, hostile, or apathetic audiences—and then to do it again the next day. And yet, over the course of the book’s multidecade arc, Grubbs depicts music making as an irreversible process—one reason for loving it so.
Rapid In-situ Growth of Oxygen-defect Rich Fe(OH)3@Co(OH)2@NF Nanoarray as Efficient OER Electrocatalyst
Authors: Zhang Mengyuan , Zhou Lina , Du Xuena , Huang Xianmin , Liu Hui , Wang Qingbo , Guo Long , Wang Hai
Published: February 2022

In this work, oxygen-defect rich Fe(OH)3@Co(OH)2@NF nanoarray (which is denoted as FCN) was synthesized via a facile sacrificial template-accelerated hydrolysis (STAH) method. The introduced oxygen vacancies during the incorporation of Fe3+ reduced the adsorption barrier of -OH, and enhanced the conductivity of the material. In addition, morphology and phase transformation, amorphous regions between the crystalline heterojunction surfaces give FCN nanoarray higher surface area with more active sites, which enhances the oxygenation performance. Consequently, oxygen-defect rich FCN nanoarray possessed a low OER overpotential of 225.8 mV at 50 mA cm−2.
Dynamic Regret Avoidance
Authors: Fioretti Michele , Vostroknutov Alexander , Coricelli Giorgio
Published: February 2022

In a stock market experiment, we examine how regret avoidance influences the decision to sell an asset while its price changes over time. Participants know beforehand whether they will observe the future prices after they sell the asset or not. Without future prices, participants are affected only by regret about previously observed high prices (past regret), but when future prices are available, they also avoid regret about expected after-sale high prices (future regret). Moreover, as the relative sizes of past and future regret change, participants dynamically switch between them. This demonstrates how multiple reference points dynamically influence sales. (JEL C91, G12, G41)
Trust Building in Credence Goods Markets
Authors: Fong Yuk-fai , Liu Ting , Meng Xiaoxuan
Published: February 2022

We study trust building in credence-goods markets in a dynamic setting. When consumers’ expected loss is low and it is efficient to fix only the more severe problem, there is no trade in the one-shot game. In the repeated game, an expert’s honesty is monitored through consumers’ rejection of his recommendations. The expert’s profit in the optimal equilibrium weakly increases in the discount factor but does not achieve the first best, which contrasts sharply with the optimal equilibrium in experience-goods markets. The optimal equilibrium involves undertreatment if the expert is sufficiently patient, and overtreatment if he is moderately patient. (JEL C73, D82, D83, Z13)
Regulating Product Communication
Authors: Janssen Maarten C.W. , Roy Santanu
Published: February 2022

Information regulation that penalizes deceptive communication by firms can have significant unintended consequences. We consider a market where competing firms communicate private information about product quality through a combination of pricing and direct communication (advertising or labeling) that may be false. A higher fine for lying reduces the reliance on price signaling, thereby lowering market power and consumption distortions; however, it may lead to excessive disclosure. Low fines are always worse than no fines. High fines are welfare improving only if communication itself is inexpensive. Penalizing false claims may reduce profits of both high- and low-quality firms. (JEL D21, D83, L25, M37)
Showing Off or Laying Low? The Economics of Psych-outs
Authors: Denter Philipp , Morgan John , Sisak Dana
Published: February 2022

We analyze the incentives for showing off, which we model as a costly signaling game, and study the consequences of norms against such behavior. Prior to competing in a contest, a newcomer can signal his talent to an incumbent. In equilibrium, costly signaling of ability occurs only when the newcomer is exceptionally talented. In such situations signaling benefits both contestants: the newcomer for obvious reasons; the incumbent by economizing on wasted effort in the contest. Our results rationalize the emergence of norms against showing off in settings where total effort is important. When selection efficiency matters, such norms decrease welfare. (JEL D82, D83, D91, Z13)