bluuebunny/crossref_metadata_2025 huggingface dataset:
A retrospective study on the clinical characteristics and prognosis of alopecia totalis and universalis: An update on prognosis
Authors: Choi Sang‐Min , Kang Min‐Jeong , Kwon Soon‐Hyo , Sim Woo‐Young , Lew Bark‐Lynn
Published: May 2023

Alopecia totalis (AT) and alopecia universalis (AU) is known to have a poor prognosis with high relapse rate, and treatment failure is observed in most patients, regardless of the type of therapy. Although treatment and the prognosis of AT and AU have improved in recent years, old data are routinely cited in recent review papers without questioning them. The authors aimed to study the clinical characteristics and prognosis of AT and AU to update and compare the results with those of previously reported studies. The authors retrospectively reviewed patients diagnosed with AT and AU from 2006 to 2017 in a single institution. Of the 419 patients, the mean age at first episode was 22.9 years, and 24.6% had early onset (≤13 years). During follow‐up, 53.9% had more than 50% hair growth, and 19.6% of patients showed >90% hair growth. Among patients who showed >50% improvement, 36.7% had no recurrence. In early studies conducted in the 1950s and 1960s, the chance of full hair regrowth was reported to be <10%. In our study, patients with >90% improvement in AT and AU accounted for 19.6% of patients. The authors provide an update on data regarding the prognoses of AT and AU.
Abiotic and biotic factors reduce the viability of a high‐elevation salamander in its native range
Authors: Campbell Grant Evan H. , DiRenzo Graziella V. , Brand Adrianne B.
Published: May 2023

Amphibian populations are undergoing worldwide declines, and high‐elevation, range‐restricted amphibian species may be particularly vulnerable to environmental stressors. In particular, future climate change may have disproportional impacts to these ecosystems. Evaluating the combined effects of abiotic changes and biotic interactions simultaneously is important for forecasting the range of future outcomes. This information is necessary to aid conservation decision‐making.

We use field data to estimate population demographic parameters for an exemplary high‐elevation amphibian species, the federally endangered Shenandoah salamanderPlethodon shenandoah. These parameters were entered into a Markov projection model which we used to forecast the future population status of the Shenandoah salamander.

We found that if the population maintains its current site colonization and persistence rates, it is at the risk of extinction that could be exacerbated by both climate and interspecific competition.

Synthesis and applications.Managers have a fundamental objective directed by official policy of maintaining the species ‘for the foreseeable future’. Our evaluation of multiple hypotheses about population drivers reveals that extinction is projected for this species. Our analysis suggests that considering active management need not depend on resolving the uncertainty.
Advancing healthcare equity through dissemination and implementation science
Authors: Baumann Ana A. , Shelton Rachel C. , Kumanyika Shiriki , Haire‐Joshu Debra
Published: May 2023

Objective

To provide guiding principles and recommendations for how approaches from the field of dissemination and implementation (D&I) science can advance healthcare equity.

Data Sources and Study Setting

This article, part of a special issue sponsored by the Agency for Healthcare Research and Quality (AHRQ), is based on an outline drafted to support proceedings of the 2022 AHRQ Health Equity Summit and further revised to reflect input from Summit attendees.

Study Design

This is a narrative review of the current and potential applications of D&I approaches for understanding and advancing healthcare equity, followed by discussion and feedback with Summit attendees.

Data Collection/Extraction Methods

We identified major themes in narrative and systematic reviews related to D&I science, healthcare equity, and their intersections. Based on our expertise, and supported by synthesis of published studies, we propose recommendations for how D&I science is relevant for advancing healthcare equity. We used iterative discussions internally and at the Summit to refine preliminary findings and recommendations.

Principal Findings

We identified four guiding principles and three D&I science domains with strong promise for accelerating progress toward healthcare equity. We present eight recommendations and more than 60 opportunities for action by practitioners, healthcare leaders, policy makers, and researchers.

Conclusions

Promising areas for D&I science to impact healthcare equity include the following: attention to equity in the development and delivery of evidence‐based interventions; the science of adaptation; de‐implementation of low‐value care; monitoring equity markers; organizational policies for healthcare equity; improving the economic evaluation of implementation; policy and dissemination research; and capacity building.
The selective regulation of immune responses by matrix metalloproteinase MMP14 in Ostrinia furnacalis
Authors: Chen Kangkang , Lu Shiqi , Song Jiahui , Dou Xiaoyi , Wei Xiangyi , Wang Xinyan , Liu Xu , Feng Congjing
Published: May 2023

Matrix metalloproteinases (MMPs) are crucial for tissue remodeling and immune responses in insects, yet it remains unclear how MMPs affect the various immune processes against pathogenic infections and whether the responses vary among insects. In this study, we used the lepidopteran pest Ostrinia furnacalis larvae to address these questions by examining the changes of immune‐related gene expression and antimicrobial activity after the knockdown of MMP14 and bacterial infections. We identified MMP14 in O. furnacalis using the rapid amplification of complementary DNA ends (RACE), and found that it was conserved and belonged to the MMP1 subfamily. Our functional investigations revealed that MMP14 is an infection‐responsive gene, and its knockdown reduces phenoloxidase (PO) activity and Cecropin expression, while the expressions of Lysozyme, Attacin, Gloverin, and Moricin are enhanced after MMP14 knockdown. Further PO and lysozyme activity determinations showed consistent results with gene expression of these immune‐related genes. Finally, the knockdown of MMP14 decreased larvae survival to bacterial infections. Taken together, our data indicate that MMP14 selectively regulates the immune responses, and is required to defend against bacterial infections in O. furnacalis larvae. Conserved MMPs may serve as a potential target for pest control using a combination of double‐stranded RNA and bacterial infection.
Is there a relationship between enchytraeids diversity and community with soybean (Glycine maxL.) productivity in no‐till system in subtropical soils ofBrazil?
Authors: Kraft Elston , Alexandre Douglas , de Oliveira Filho Luís Carlos Iuñes , Baretta Carolina Riviera Duarte Maluche , Klauberg‐Filho Osmar , Baretta Dilmar
Published: May 2023

The relationship between the productivity of crops of agricultural interest and their interactions with physicochemical soil properties is widely explored. However, there is still a gap concerning the contribution of biological soil attributes and especially the relationship between crop productivity and the structures of organism communities within the soil, such as the enchytraeids. This paper aimed to evaluate the diversity and structures of enchytraeids communities in subtropical soils and their relationship with soybean productivity and soil properties within a no‐tillage system. This study was conducted in soybean growing grounds working under no‐till farming systems in southern Brazil. Samples were collected according to ISO 23611‐3 and extracted with the hot–wet methodology. The organisms were identified up to their genus level. Enchytraeids density increased with the increase of soybean productivity for both evaluated crops.Enchytraeus,Fridericia, andHemienchytraeuswere more abundant in high productivity and genusAchaetawas only found in the second crop and was not a sensitive indicator toward changes in soybean productivity. Regarding the relationship between the enchytraeid community and soil attributes, the variables clay, phosphorus, moisture contents, pH, Ca/Mg as well as carbon and nitrogen from soil and litter, affected Enchytraeidae distribution. Enchytreids showed significant correlations with soybean productivity in the no‐tillage system for subtropical soils in Brazil, demonstrating potential bioindicators of soil quality and consequently of soybean productivity.
Hyperepilithics—An overlooked life form of vascular plants on tropical vertical rock walls
Authors: Couto Dayvid R. , Porembski Stefan , Barthlott Wilhelm , de Paula Luiza F. A.
Published: May 2023

Vascular epiphytes are a characteristic life form in many tropical regions and often occur growing on bare rocks. South America has the highest diversity. Here, we describe a neglected life form: hyperepilithics adapted and restricted to growing on vertical (inclination above 70°) and bare rock walls without having roots intruding the substrate. Hyperepilithics are in particular present on Brazilian inselbergs and dominated by highly specialized Bromeliaceae, mainly of the genera Stigmatodon, Tillandsia and Alcantarea, whereas Orchidaceae surprisingly has a low representation. An overview of this habitat, the life form hyperepilithics and a comparison with similar paleotropical habitats (mainly inselbergs in Western/Eastern Africa and India) are provided. Attention is drawn to hyperepilithics as a most promising and not yet exploited source for a sustainable urban ‘vertical gardening’, for example in tropical megacities.
Decentering death: The war on terror and the less‐than‐lethal paradigm
Authors: Rubaii Kali
Published: May 2023

How does violent military coercion work alongside liberal democratic values in contemporary iterations of imperialism? This article shows how the less‐than‐lethal paradigm occludes death and perpetuates extreme forms of both deadly and not‐deadly military coercion in Iraq. Key to the 2003 invasion and subsequent counterinsurgency in Iraq, the less‐than‐lethal paradigm extends across military doctrine and US popular discourse. Based on the idea that killing is an undesirable way to dominate, the less‐than‐lethal paradigm is not necessarily benevolent or less deadly; instead, it is a legal, discursive, and logistical maneuver to minimize the political power of death and dying on the global stage. Decentering death, the less‐than‐lethal paradigm rebrands violence by reframing war as a precondition for peace, minimizing killing and death, disseminating nonkilling forms of coercion, and assigning responsibility to others for violence.
Is 10 cm ileal resection sufficient in locally advanced caecal cancer surgery?
Authors: Baik HyungJoo , Kim Jihyeong , Shin Jin Yong , Kim Kwang Hee , Seo Sang Hyuk , Kang Sang Hyun , Lee Hee Ju , Namkoong Kyung , Oh Min Kyung , An Min Sung
Published: May 2023

Background

There is no consensus as to how much ileal resection is sufficient when performing a right hemicolectomy for right colon cancers. Locally advanced caecal cancer has the highest incidence of peri‐ileal lymph node metastasis. Therefore, this study investigated whether the 10 cm ileum resection suggested by the Japanese Society for Cancer of the Colon and Rectum is oncologically safe in stage II and III caecal cancer.

Methods

The prospectively collected medical records of stage II and III caecal cancer patients who underwent a right hemicolectomy with at least D2 lymph node dissection were reviewed retrospectively. The patients were divided into two groups according to the length of proximal ileal resected: group 1 (≤10 cm) and group 2 (>10 cm). Factors contributing to the 5‐year overall survival (OS) were analysed.

Results

The study enrolled 89 patients with pathological stage II or III caecal cancer. The >10 cm group tended to be younger (P = 0.0938) with higher pathological N stages (P = 0.0899) than the ≤10 cm group. The 5‐year OS did not differ between the two groups. No significant difference was found between the two groups according to stage. Age (HR = 1.06, 95% CI = 1.02–1.10, P = 0.0069) and N2 stage (HR = 5.38, 95% CI = 1.90–15.28, P = 0.0016) were significantly associated with OS in both uni‐ and multivariate analyses.

Conclusions

There was no OS benefit to resecting >10 cm of ileum in either stage II or III caecal cancer patients. Hence, we suggest that the ‘10 cm rule’ is sufficient for stage II and III caecal cancer patients.
Understanding unplanned return to theatre in rural South Australia general surgery: review of four major hospitals over a six‐year period
Authors: Liu Jianliang , Ow Yeong Yu Xiang , Bradshaw Emma , Bruening Martin , Anthony Adrian , Trochsler Markus , Edwards Suzanne , Maddern Guy
Published: May 2023

Background

Unplanned return to theatre (URTT) is associated with longer hospital stay and higher mortality rates, placing extra burden on hospital resources. There is a lack of literature analysing causes of URTT in a rural general surgery department. This knowledge may be important to help identify patients at risk of URTT. This study aims to identify causes of URTT in rural general surgical patients.

Methods

This is a retrospective multicenter cohort involving four rural South Australian (SA) hospitals: Mount Gambier (MGH), Whyalla (WH), Port Augusta (PAH), and Port Lincoln (PLH). All general surgical inpatients admitted from February 2014 to March 2020 were analysed to identify all‐cause of URTT.

Results

Of the 44 191 surgical procedures performed, there were 67 (0.15%) URTT. The most common surgical subspecialty cases that resulted in URTT were Colorectal (47.1%), General surgery (33.2%) Plastics (9.8%), and Hepatopancreatico‐biliary (3.9%). The three commonest operations during URTT were washouts 22 (32.8%), interventions for haemostasis 11 (16.4%) and bowel resections 9 (13.4%). Sixteen (24%) of URTT followed emergency surgery. When comparing between elective and emergency admissions needing URTT, there were no statistical difference in age, gender, speciality type, types of surgery performed, and median number of days until URTT.

Conclusion

Rates of URTT are low in South Australian rural hospitals when compared to our overseas counterpart. A wide range of surgery is being performed in rural centres, further supporting the need for rural surgical trainees to have a tailored curriculum encompassing subspecialities and being competent in managing any potential complications.
Factors affecting timeliness in management of head and neck cancer
Authors: Kwok Matthew Ming Kei , Wong Amy , Prasad Jessica
Published: May 2023

Background

Timeliness in the management of patients with head and neck cancer (HNC) can be affected by both patient and non‐patient related factors. This study aims to investigate the factors associated with the timeliness of managing HNC.

Methods

A retrospective review was conducted on Western Health medical records including all new patients presenting to the Western Health HNC surgical outpatient clinic in the five‐year period from first January 2017 to 31st December 2021 with the diagnosis of a HNC. Both patient and non‐patient related factors were compared with the duration between a patient's referral to a HNC service and the commencement of their treatment.

Results

Two hundred and twenty‐eight patients were included in this study. The median duration from referral to the commencement of treatment was 48 days. Lack of radiological or pathological investigations prior to referral to a HNC service as well as early staging were found to significantly impact timeliness in management. Socioeconomic factors such as non‐English speaking backgrounds, distance from the hospital and lack of social supports were not found to negatively impact timeliness of management.

Conclusion

The management of patients with HNC require careful consideration of all patient and non‐patient related factors which may affect timeliness in management, particularly investigations performed prior to their referral to a HNC service.
Genetically instrumented LDL‐cholesterol lowering and multiple disease outcomes: A Mendelian randomization phenome‐wide association study in the UK Biobank
Authors: Pham Kitty , Mulugeta Anwar , Lumsden Amanda , Hyppӧnen Elina
Published: May 2023

Aims

Lipid‐lowering medications are widely used to control blood cholesterol levels and manage a range of cardiovascular and lipid disorders. We aimed to explore the possible associations between LDL lowering and multiple disease outcomes or biomarkers.

Methods

We performed a Mendelian randomization phenome‐wide association study (MR‐PheWAS) in 337 475 UK Biobank participants to test for associations between four proposed LDL‐C‐lowering genetic risk scores (PCSK9, HMGCR, NPC1L1 and LDLR) and 1135 disease outcomes, with follow‐up MR analyses in 52 serum, urine, imaging and clinical biomarkers. We used inverse‐variance weighted MR in the main analyses and complementary MR methods (weighted median, weighted mode, MR‐Egger and MR‐PRESSO) as sensitivity analyses. We accounted for multiple testing with false discovery rate correction (P < 2.0 × 10−4 for phecodes, P < 1.3 × 10−2 for biomarkers).

Results

We found evidence for an association between genetically instrumented LDL lowering and 10 distinct disease outcomes, suggesting potential causality. All genetic instruments were associated with hyperlipidaemias and cardiovascular diseases in the expected directions. Biomarker analyses supported an effect of LDL‐C lowering through PCSK9 on lung function (FEV [beta per 1 mg/dL lower LDL‐C −1.49, 95% CI −2.21, −0.78]; FVC [−1.42, 95% CI −2.29, −0.54]) and through HMGCR on hippocampal volume (beta per 1 mg/dL lower LDL‐C 6.09, 95% CI 1.74, 10.44).

Conclusions

We found genetic evidence to support both positive and negative effects of LDL‐C lowering through all four LDL‐C‐lowering pathways. Future studies should further explore the effects of LDL‐C lowering on lung function and changes in brain volume.
The role of NMDA receptors in bipolar disorder: A systematic review
Authors: Weiss Francesco , Caruso Valerio , De Rosa Ugo , Beatino Maria Francesca , Barbuti Margherita , Nicoletti Ferdinando , Perugi Giulio
Published: May 2023

Objectives

Glutamatergic transmission and N‐methyl‐D‐aspartate receptors (NMDARs) have been implicated in the pathophysiology schizophrenic spectrum and major depressive disorders. Less is known about the role of NMDARs in bipolar disorder (BD). The present systematic review aimed to investigate the role of NMDARs in BD, along with its possible neurobiological and clinical implications.

Methods

We performed a computerized literature research on PubMed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement, using the following string: ((“Bipolar Disorder”[Mesh]) OR (manic‐depressive disorder[Mesh]) OR (“BD”) OR (“MDD”)) AND ((NMDA [Mesh]) OR (N‐methyl‐D‐aspartate) OR (NMDAR[Mesh]) OR (N‐methyl‐D‐aspartate receptor)).

Results

Genetic studies yield conflicting results, and the most studied candidate for an association with BD is the GRIN2B gene. Postmortem expression studies (in situ hybridization and autoradiographic and immunological studies) are also contradictory but suggest a reduced activity of NMDARs in the prefrontal, superior temporal cortex, anterior cingulate cortex, and hippocampus.

Conclusions

Glutamatergic transmission and NMDARs do not appear to be primarily involved in the pathophysiology of BD, but they might be linked to the severity and chronicity of the disorder. Disease progression could be associated with a long phase of enhanced glutamatergic transmission, with ensuing excitotoxicity and neuronal damage, resulting into a reduced density of functional NMDARs.
Integrating cognitive load theory with other theories, within and beyond educational psychology
Authors: Hanham José , Castro‐Alonso Juan Cristobal , Chen Ouhao
Published: May 2023

Background and Aims

The long‐standing aim of cognitive load theory (CLT) has been to generate instructional design principles that show teachers how to instruct students effectively, based on knowledge of the intricacies of human cognitive architecture. Historically, the focus of CLT has been on identifying cognitive processes related to learning and instruction. However, the theory has become more multidisciplinary over time, drawing on theoretical perspectives both within, and beyond, educational psychology.

Results

This Editorial presents a brief historical overview of key developments in CLT and seven key themes that are pertinent to research on CLT. These themes are as follows: Level of Expertise, Cognitive Load Measurement, Embodied Cognition, Self‐Regulated Learning, Emotion Induction, Replenishment of Working Memory, and Two Subprocessors of Working Memory. Summaries of the nine empirical contributions to the special issue are presented and discussed in relation to how they provide insight into one or more of these themes.

Conclusions

Understanding the variables that impact student learning and instruction has always represented the core aim of CLT. The growing multidisciplinary features of CLT should provide researchers and practitioners with more holistic perspectives of the factors that predict student learning and, in turn, guide instructional design.
Learning to work with the black box: Pedagogy for a world with artificial intelligence
Authors: Bearman Margaret , Ajjawi Rola
Published: May 2023

Artificial intelligence (AI) is increasingly integrating into our society. University education needs to maintain its relevance in an AI‐mediated world, but the higher education sector is only beginning to engage deeply with the implications of AI within society. We define AI according to a relational epistemology, where,in the context of a particular interaction,acomputational artefact provides a judgement about an optimal course of action and that this judgement cannot be traced. Therefore, by definition, AI must always act as a ‘black box’. Rather than seeking to explain ‘black boxes’, we argue that a pedagogy for an AI‐mediated world involves learning to work with opaque, partial and ambiguous situations, which reflect the entangled relationships between people and technologies. Such a pedagogy asks learners locate AI as socially bounded, where AI is always understood within the contexts of its use. We outline two particular approaches to achieve this: (a) orienting students to quality standards that surround AIs, what might be called the tacit and explicit ‘rules of the game’; and (b) providing meaningful interactions with AI systems.

Practitioner notes

What is already known about this topic

Artificial intelligence (AI) is conceptualised in many different ways but is rarely defined in the higher education literature.

Experts have outlined a range of graduate capabilities for working in a world of AI such as teamwork or ethical thinking.

The higher education literature outlines an imperative need to respond to AI, as underlined by recent commentary on ChatGPT.

What this paper adds

A definition of an AI that is relational: A particular interaction where a computational artefact provides a judgement about an optimal course of action, which cannot be easily traced.

Focusing onworking withAI black boxes rather than trying tosee insidethe technology.

Describing a pedagogy for an AI‐mediated world that promotes working in complex situations with partial and indeterminate information.

Implications for practice and/or policy

Focusing on quality standards helps learners understand the social regulating boundaries around AI.

Promoting learner interactions with AI as part of a sociotechnical ensemble helps build evaluative judgement in weighting AI's contribution to work.

Asking learners to work with AI systems prompts understanding of the evaluative, ethical and practical necessities of working with a black box.
COVID‐19 in Chihuahua, Mexico: Assessing its spatial behaviour through the inverse distance weighted interpolation technique
Authors: Ibarra‐Bonilla Jesús S. , Villarreal‐Guerrero Federico , Pinedo‐Alvarez Alfredo , Prieto‐Amparán Jesús A.
Published: May 2023

This study focused on the spatial evolution of COVID‐19 in the state of Chihuahua, Mexico. Data were retrieved from governmental databases and analyzed by means of GIS, applying the inverse distance weighted (IDW) method. The period of December 2019 through November 2021 was split into eight seasons. The root mean square error (RMSE) was used to assess the reliability of the interpolations, showing acceptable values (RSME < 25). During the period, the municipalities of Juarez and Chihuahua reached the highest number of confirmed cases and deaths, Juarez being the main hotspot of contagion (37.2% of confirmed cases; 46.9% of deaths). Four waves of contagion were identified during the evaluated period, with Fall 2020 being the strongest season. Since Fall 2020, the spread of the disease was more often observed in municipalities with the highest human mobility. Although the spread of COVID‐19 decreased after Spring 2021, in Fall 2021 records indicated a continuous increase in cases in the state. That could be due to a relaxation of the implementation of sanitary measures, as well as to the propagation of novel COVID‐19 variants having an elevated infectious level. Geospatial techniques allowed for an understanding of the spatial spread of COVID‐19 and could be useful for its control.
Novel and efficient method for culturing patient‐derived gastric cancer stem cells
Authors: Morimoto Tomonori , Takemura Yukitoshi , Miura Takemitsu , Yamamoto Takehito , Kakizaki Fumihiko , An Hideo , Maekawa Hisatsugu , Yamaura Tadayoshi , Kawada Kenji , Sakai Yoshiharu , Yuba Yoshiaki , Terajima Hiroaki , Obama Kazutaka , Taketo Makoto Mark , Miyoshi Hiroyuki
Published: May 2023

Experimental techniques for patient‐derived cancer stem‐cell organoids/spheroids can be powerful diagnostic tools for personalized chemotherapy. However, establishing their cultures from gastric cancer remains challenging due to low culture efficiency and cumbersome methods. To propagate gastric cancer cells as highly proliferative stem‐cell spheroids in vitro, we initially used a similar method to that for colorectal cancer stem cells, which, unfortunately, resulted in a low success rate (25%, 18 of 71 cases). We scrutinized the protocol and found that the unsuccessful cases were largely caused by the paucity of cancer stem cells in the sampled tissues as well as insufficient culture media. To overcome these obstacles, we extensively revised our sample collection protocol and culture conditions. We then investigated the following second cohort and, consequently, achieved a significantly higher success rate (88%, 29 of 33 cases). One of the key improvements included new sampling procedures for tumor tissues from wider and deeper areas of gastric cancer specimens, which allowed securing cancer stem cells more reproducibly. Additionally, we embedded tumor epithelial pieces separately in both Matrigel and collagen type‐I as their preference to the extracellular matrix was different depending on the tumors. We also added a low concentration of Wnt ligands to the culture, which helped the growth of occasional Wnt‐responsive gastric cancer stem‐cell spheroids without allowing proliferation of the normal gastric epithelial stem cells. This newly improved spheroid culture method may facilitate further studies, including personalized drug‐sensitivity tests prior to drug therapy.
Synthesis of novel 5‐amido‐2‐carboxypyrazines as inhibitors of the type three secretion system of Salmonella enterica serovar Typhimurium
Authors: Li Zhenyu , Su Jiahang , Liu Zhiyong , Shen Yuemao , Tang Hui
Published: May 2023

A series of novel 5‐amido‐2‐carboxypyrazine derivatives were designed, synthesized and evaluated for the inhibitory activities against the T3SS of Salmonella enterica serovar Typhimurium. Preliminary results displayed that the compounds 2f, 2g, 2h and 2i showed potent inhibitory activities against T3SS. Compound 2h was identified as the most potent T3SS inhibitor and the SPI‐1 effector secretion was strongly inhibited by 2h in a dose‐dependent manner. The effects of compound 2h on the SPI‐1 genes transcription might be via impacting the SicA/InvF regulatory pathway.
Scalable and Efficient Functional Map Computations on Dense Meshes
Authors: Magnet Robin , Ovsjanikov Maks
Published: May 2023

We propose a new scalable version of the functional map pipeline that allows to efficiently compute correspondences between potentially very dense meshes. Unlike existing approaches that process dense meshes by relying on ad‐hoc mesh simplification, we establish an integrated end‐to‐end pipeline with theoretical approximation analysis. In particular, our method overcomes the computational burden of both computing the basis, as well the functional and pointwise correspondence computation by approximating the functional spaces and the functional map itself. Errors in the approximations are controlled by theoretical upper bounds assessing the range of applicability of our pipeline. With this construction in hand, we propose a scalable practical algorithm and demonstrate results on dense meshes, which approximate those obtained by standard functional map algorithms at the fraction of the computation time. Moreover, our approach outperforms the standard acceleration procedures by a large margin, leading to accurate results even in challenging cases.
Reciprocal interaction between mitochondrial fission and mitophagy in postoperative delayed neurocognitive recovery in aged rats
Authors: Li Yitong , Li Yue , Chen Lei , Li Yi , Liu Kaixi , Hong Jingshu , Wang Qian , Kang Ning , Song Yanan , Mi Xinning , Yuan Yi , Han Dengyang , Liu Taotao , Yang Ning , Guo Xiangyang , Li Zhengqian
Published: May 2023

Introduction

Emerging evidence suggests that mitochondrial dysfunction plays a crucial role in the pathogenesis of postoperative delayed neurocognitive recovery (dNCR). Mitochondria exist in a dynamic equilibrium that involves fission and fusion to regulate morphology and maintains normal cell function via the removal of damaged mitochondria through mitophagy. Nonetheless, the relationship between mitochondrial morphology and mitophagy, and how they influence mitochondrial function in the development of postoperative dNCR, remains poorly understood. Here, we observed morphological alterations of mitochondria and mitophagy activity in hippocampal neurons and assessed the involvement of their interaction in dNCR following general anesthesia and surgical stress in aged rats.

Methods

Firstly, we evaluated the spatial learning and memory ability of the aged rats after anesthesia/surgery. Hippocampal mitochondrial function and mitochondrial morphology were detected. Afterwards, mitochondrial fission was inhibited by Mdivi‐1 and siDrp1 in vivo and in vitro separately. We then detected mitophagy and mitochondrial function. Finally, we used rapamycin to activate mitophagy and observed mitochondrial morphology and mitochondrial function.

Results

Surgery impaired hippocampal‐dependent spatial learning and memory ability and caused mitochondrial dysfunction. It also increased mitochondrial fission and inhibited mitophagy in hippocampal neurons. Mdivi‐1 improved mitophagy and learning and memory ability of aged rats by inhibiting mitochondrial fission. Knocking down Drp1 by siDrp1 also improved mitophagy and mitochondrial function. Meanwhile, rapamycin inhibited excessive mitochondrial fission and improved mitochondrial function.

Conclusion

Surgery simultaneously increases mitochondrial fission and inhibits mitophagy activity. Mechanistically, mitochondrial fission/fusion and mitophagy activity interact reciprocally with each other and are both involved in postoperative dNCR. These mitochondrial events after surgical stress may provide novel targets and modalities for therapeutic intervention in postoperative dNCR.
Dopamine D1‐receptor‐expressing pathway from the nucleus accumbens to ventral pallidum‐mediated sevoflurane anesthesia in mice
Authors: Zhang Jie , Peng Yiting , Liu Chengxi , Zhang Yu , Liang Xiaoli , Yuan Chengdong , Shi Wenyan , Zhang Yi
Published: May 2023

Background

General anesthesia has long been used in clinical practice, but its precise pharmacological effects on neural circuits are not fully understood. Recent investigations suggest that the sleep–wake system may play a role in the reversible loss of consciousness induced by general anesthetics. Studies in mice have shown that microinjection of dopamine receptor 1 (D1R) agonists into the nucleus accumbens (NAc) promotes recovery from isoflurane anesthesia, while microinjection of D1R antagonists has the opposite effect. Furthermore, during the induction and maintenance of sevoflurane anesthesia, there is a significant decrease in extracellular dopamine levels in the NAc, which subsequently increases during the recovery period. These findings suggest the involvement of the NAc in the regulation of general anesthesia. However, the specific role of D1R‐expressing neurons in the NAc during general anesthesia and the downstream effect pathways are still not well understood.

Methods

In order to analyze the impact of sevoflurane anesthesia on NAcD1R neurons and the NAcD1R‐VP pathway, this study employed calcium fiber photometry to investigate alterations in the fluorescence intensity of calcium signals in dopamine D1‐receptor‐expressing neurons located in the nucleus accumbens (NAcD1R neurons) and the NAcD1R‐VP pathway during sevoflurane anesthesia. Subsequently, optogenetic techniques were utilized to activate or inhibit NAcD1R neurons and their synaptic terminals in the ventral pallidum (VP), aiming to elucidate the role of NAcD1R neurons and the NAcD1R‐VP pathway in sevoflurane anesthesia. These experiments were supplemented with electroencephalogram (EEG) recordings and behavioral tests. Lastly, a genetically‐encoded fluorescent sensor was employed to observe changes in extracellular GABA neurotransmitters in the VP during sevoflurane anesthesia.

Results

Our findings revealed that sevoflurane administration led to the inhibition of NAcD1R neuron population activity, as well as their connections within the ventral pallidum (VP). We also observed a reversible reduction in extracellular GABA levels in the VP during both the induction and emergence phases of sevoflurane anesthesia. Additionally, the optogenetic activation of NAcD1R neurons and their synaptic terminals in the VP resulted in a promotion of wakefulness during sevoflurane anesthesia, accompanied by a decrease in EEG slow wave activity and burst suppression rate. Conversely, the optogenetic inhibition of the NAcD1R‐VP pathway exerted opposite effects.

Conclusion

The NAcD1R‐VP pathway serves as a crucial downstream pathway of NAcD1R neurons, playing a significant role in regulating arousal during sevoflurane anesthesia. Importantly, this pathway appears to be associated with the release of GABA neurotransmitters from VP cells.
Delayed CO2 postconditioning promotes neurological recovery after cryogenic traumatic brain injury by downregulating IRF7 expression
Authors: Li Yan , Chen Ru , Shen Gui‐Ping , Yin Jing , Li Yu , Zhao Jing , Nan Fang , Zhang Shu‐Han , Zhang Hui‐Feng , Yang Cai‐Hong , Wu Mei‐Na , Fan Yan‐Ying
Published: May 2023

Aims

Few treatments are available in the subacute phase of traumatic brain injury (TBI) except rehabilitation training. We previously reported that transient CO2 inhalation applied within minutes after reperfusion has neuroprotective effects against cerebral ischemia/reperfusion injury. In this study, it was hypothesized that delayed CO2 postconditioning (DCPC) starting at the subacute phase may promote neurological recovery of TBI.

Methods

Using a cryogenic TBI (cTBI) model, mice received DCPC daily by inhaling 5%/10%/20% CO2 for various time‐courses (one/two/three cycles of 10‐min inhalation/10‐min break) at Days 3–7, 3–14 or 7–18 after cTBI. Beam walking and gait tests were used to assess the effect of DCPC. Lesion size, expression of GAP‐43 and synaptophysin, amoeboid microglia number and glia scar area were detected. Transcriptome and recombinant interferon regulatory factor 7 (Irf7) adeno‐associated virus were applied to investigate the molecular mechanisms.

Results

DCPC significantly promoted recovery of motor function in a concentration and time‐course dependent manner with a wide therapeutic time window of at least 7 days after cTBI. The beneficial effects of DCPC were blocked by intracerebroventricular injection of NaHCO3. DCPC also increased puncta density of GAP‐43 and synaptophysin, and reduced amoeboid microglia number and glial scar formation in the cortex surrounding the lesion. Transcriptome analysis showed many inflammation‐related genes and pathways were altered by DCPC, and Irf7 was a hub gene, while overexpression of IRF7 blocked the motor function improvement of DCPC.

Conclusions

We first showed that DCPC promoted functional recovery and brain tissue repair, which opens a new therapeutic time window of postconditioning for TBI. Inhibition of IRF7 is a key molecular mechanism for the beneficial effects of DCPC, and IRF7 may be a potential therapeutic target for rehabilitation after TBI.
Search for the best alternative: An experimental approach
Authors: Özkan‐Seely Gülru F. , Hall David C. , Hutchison‐Krupat Jeremy
Published: May 2023

Effectively implementing any dimension of a company's strategy requires a careful balance between ensuring a sufficient number of opportunities have been explored and the execution has taken place in a timely manner for a specific initiative. Naturally, the importance of specific characteristics of an initiative will vary according to the strategic objective. Alternatives vary in their likelihood of success, how sensitive their value is to time, and the resources required to explore additional options. Extant research has established optimal rules for what constitutes a sufficient degree of exploration, and how to go about exploring alternatives. Yet, how individuals vary their behavior according to the characteristics of an initiative is not well understood. We use a controlled experiment to study how individuals' decisions are impacted by these characteristics. As expected, individuals perform significantly worse than optimal behavior would predict. However, the underlying drivers of this performance deviation critically depend on the characteristics of the initiative. Individuals who face simple initiatives that lack sensitivity to time tend to evaluate far too many options. In contrast, when a simple initiative's value is sensitive to time, individuals tend to evaluate far too few options. When the individuals face more difficult initiatives, they do not exhibit such extreme tendencies in terms of how many alternatives they evaluate. Rather, for the most challenging initiatives, individuals exhibit near optimal behavior in terms of how many alternatives they evaluate. Our findings help to provide insight to managers on where they should focus their attention in terms of pushing for more or less exploration.
Time to think prime times for treatment of necrotizing pancreatitis: Pendulum conundrum
Authors: Nakai Yousuke , Hamada Tsuyoshi , Saito Tomotaka , Shiomi Hideyuki , Maruta Akinori , Iwashita Takuji , Iwata Keisuke , Takenaka Mamoru , Masuda Atsuhiro , Matsubara Saburo , Sato Tatsuya , Mukai Tsuyoshi , Yasuda Ichiro , Isayama Hiroyuki ,   for the WONDERFUL study group in Japan
Published: May 2023

Pancreatic fluid collections (PFCs) typically develop as local complications of acute pancreatitis and complicate the clinical course of patients with acute pancreatitis and potentially fatal clinical outcomes. Interventions are required in cases of symptomatic walled‐off necrosis (WON) (matured PFCs with necrosis) and pancreatic pseudocysts (matured PFCs without necrosis). In the management of necrotizing pancreatitis and WON, endoscopic ultrasound‐guided transluminal drainage combined with on‐demand endoscopic necrosectomy (i.e. the step‐up approach) is increasingly used as a less invasive treatment modality compared with a surgical or percutaneous approach. Through the substantial research efforts and development of specific devices and stents (e.g. lumen‐apposing metal stents), endoscopic techniques of PFC management have been standardized to some extent. However, there has been no consensus about timing of carrying out each treatment step; for instance, it is uncertain when direct endoscopic necrosectomy should be initiated and finished and when a plastic or metal stent should be removed following clinical treatment success. Despite emerging evidence for the effectiveness of noninterventional supportive treatment (e.g. antibiotics, nutritional support, irrigation of the cavity), there has been only limited data on the timing of starting and stopping the treatment. Large studies are required to optimize the timing of those treatment options and improve clinical outcomes of patients with PFCs. In this review, we summarize the current available evidence on the indications and timing of interventional and supportive treatment modalities for this patient population and discussed clinical unmet needs that should be addressed in future research.
The use of botulinum toxin and intrathecal baclofen in hip dysplasia in cerebral palsy
Authors: Gormley Mark
Published: May 2023

This letter to the editor is on the original article by Asma et al. on pages 1112–1117 and the letters to the editor by Graham et al. on page 1123 and Howard and Shrader on page 1124 of this issue.
Diagnostic delay in amyotrophic lateral sclerosis
Authors: Gwathmey Kelly G. , Corcia Philippe , McDermott Chris J. , Genge Angela , Sennfält Stefan , de Carvalho Mamede , Ingre Caroline
Published: May 2023

Background

Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease, and the time from symptom onset to diagnosis remains long. With the advent of disease‐modifying treatments, the need to identify and diagnose ALS in a timely fashion has never been greater.

Methods

We reviewed the literature to define the severity of ALS diagnostic delay, the various factors that contribute to this delay (including patient and physician factors), and the role that site of symptom onset plays in a patient's diagnostic journey.

Results

Diagnostic delay is influenced by general practitioners’ lack of recognition of ALS due to disease rarity and heterogenous presentations. As a result, patients are referred to non‐neurologists, have unnecessary diagnostic testing, and may ultimately be misdiagnosed. Patient factors include their illness behavior—which impacts diagnostic delay—and their site of symptom onset. Limb‐onset patients have the greatest diagnostic delay because they are frequently misdiagnosed with degenerative spine disease or peripheral neuropathy.

Conclusion

Prompt ALS diagnosis results in more effective clinical management, with earlier access to disease‐modifying therapies, multidisciplinary care, and, if desired, clinical trial involvement. Due to lack of commercially available ALS biomarkers, alternative strategies to identify and triage patients who likely have ALS must be employed. Several diagnostic tools have been developed to encourage general practitioners to consider ALS and make an urgent referral to ALS specialists, bypassing unnecessary referrals to non‐neurologists and unnecessary diagnostic workup.
Complexity and pitfalls in maximal exercise testing for persons with multiple sclerosis
Authors: Schlagheck Marit L. , Bansi Jens , Wenzel Charlotte , Kuzdas‐Sallaberger Marina , Kiesl David , Gonzenbach Roman , Zimmer Philipp
Published: May 2023

Background and purpose

Valid measurements of cardiorespiratory fitness in persons with multiple sclerosis (pwMS) are essential during inpatient rehabilitation for a precise evaluation of the current health status, for defining appropriate exercise intensities, and for evaluation of exercise intervention studies. We aim (i) to examine the proportion of pwMS who attain the American College of Sports Medicine (ACSM) criteria for maximal effort during graded cardiopulmonary exercise testing (CPET) and (ii) to provide insight into participant characteristics that limit maximal exercise performance.

Methods

This cross‐sectional study comprises a retrospective examination of ACSM criteria for maximal effort during graded CPET of n = 380 inpatient pwMS (mean age = 48 ± 11 years, 66% female). Chi‐squared or Fisher's exact tests were conducted to compare differences in the distribution of criteria achieved. Participants' characteristics were examined as potential predictors using binary logistic regression.

Results

Only 60% of the overall sample attained a respiratory exchange ratio ≥ 1.10. With regard to the definition applied, only 24% or 40% of the participants achieved an oxygen consumption plateau, and 17% or 50% attained the heart rate criterion. Forty‐six percent met at least two of three criteria. Disability status, gender, disease course, and body mass index were associated with the attainment of maximal effort.

Conclusions

Our findings suggest that a relevant proportion of inpatient pwMS do not attain common criteria utilized to verify maximal oxygen consumption. Identified predictors for criteria attainment can be used to create models to predict cardiorespiratory fitness and to optimize CPET protocols in restrictive groups of pwMS.
Deep brain stimulation of the anterior nucleus of the thalamus increases slow wave activity in non‐rapid eye movement sleep
Authors: Buenzli Jana C. , Werth Esther , Baumann Christian R. , Belvedere Anina , Renzel Roland , Stieglitz Lennart H. , Imbach Lukas L.
Published: May 2023

Objective

Previous studies suggest that intermittent deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) affects physiological sleep architecture. Here, we investigated the impact of continuous ANT DBS on sleep in epilepsy patients in a multicenter crossover study in 10 patients.

Methods

We assessed sleep stage distribution, delta power, delta energy, and total sleep time in standardized 10/20 polysomnographic investigations before and 12 months after DBS lead implantation.

Results

In contrast to previous studies, we found no disruption of sleep architecture or alterations of sleep stage distribution under active ANT DBS (p = .76). On the contrary, we observed more consolidated and deeper slow wave sleep (SWS) under continuous high‐frequency DBS as compared to baseline sleep prior to DBS lead implantation. In particular, biomarkers of deep sleep (delta power and delta energy) showed a significant increase post‐DBS as compared to baseline (36.67 ± 13.68 μV2 /Hz and 799.86 ± 407.56 μV2*s, p < .001). Furthermore, the observed increase in delta power was related to the location of the active stimulation contact within the ANT; we found higher delta power and higher delta energy in patients with active stimulation in more superior contacts as compared to inferior ANT stimulation. We also observed significantly fewer nocturnal electroencephalographic discharges in DBS ON condition. In conclusion, our findings suggest that continuous ANT DBS in the most cranial part of the target region leads to more consolidated SWS.

Significance

From a clinical perspective, these findings suggest that patients with sleep disruption under cyclic ANT DBS could benefit from an adaptation of stimulation parameters to more superior contacts and continuous mode stimulation.