bluuebunny/crossref_metadata_2025 huggingface dataset:
Benchmarking methods for detecting differential states between conditions from multi-subject single-cell RNA-seq data
Authors: Junttila Sini , Smolander Johannes , Elo Laura L
Published: July 2022

Single-cell RNA-sequencing (scRNA-seq) enables researchers to quantify transcriptomes of thousands of cells simultaneously and study transcriptomic changes between cells. scRNA-seq datasets increasingly include multisubject, multicondition experiments to investigate cell-type-specific differential states (DS) between conditions. This can be performed by first identifying the cell types in all the subjects and then by performing a DS analysis between the conditions within each cell type. Naïve single-cell DS analysis methods that treat cells statistically independent are subject to false positives in the presence of variation between biological replicates, an issue known as the pseudoreplicate bias. While several methods have already been introduced to carry out the statistical testing in multisubject scRNA-seq analysis, comparisons that include all these methods are currently lacking. Here, we performed a comprehensive comparison of 18 methods for the identification of DS changes between conditions from multisubject scRNA-seq data. Our results suggest that the pseudobulk methods performed generally best. Both pseudobulks and mixed models that model the subjects as a random effect were superior compared with the naïve single-cell methods that do not model the subjects in any way. While the naïve models achieved higher sensitivity than the pseudobulk methods and the mixed models, they were subject to a high number of false positives. In addition, accounting for subjects through latent variable modeling did not improve the performance of the naïve methods.
An efficient procedure for the recovery of DNA from formalin-fixed paraffin-embedded tissue sections
Authors: Oba Utako , Kohashi Kenichi , Sangatsuda Yuhei , Oda Yoshinao , Sonoda Koh-Hei , Ohga Shouichi , Yoshimoto Koji , Arai Yasuhito , Yachida Shinichi , Shibata Tatsuhiro , Ito Takashi , Miura Fumihito
Published: July 2022

With the advent of new molecular diagnostic techniques, retrieving DNA from the formalin-fixed paraffin-embedded (FFPE) tissues has become an essential yet challenging step for efficient downstream processes. Owing to low quality and quantity of DNA retrieved from the FFPE sections, the process is often impractical and needs significant improvements. Here, we established an efficient method for the purification of DNA from FFPE specimens by optimizing incubation temperature, incubation time, and the concentration of a formalin scavenger tris(hydroxymethyl)aminomethane (Tris) for reverse-crosslinking. The optimized method, named “Highly concentrated Tris-mediated DNA extraction” (HiTE), yielded three times the DNA yield per tissue slice compared with a representative DNA extraction kit. Moreover, the use of HiTE-extracted DNA increased the yield of the sequencing library three times and accordingly yielded a log higher and more reproducible sequencing library compared with that obtained using the commonly used commercial kit. The sequencing library prepared from HiTE-extracted FFPE-DNA had longer inserts and produced reads that evenly covered the reference genome. Successful application of HiTE-extracted FFPE-DNA for whole-genome and targeted gene panel sequencing indicates its practical usability.
The New Validity Rules in Chinese Civil Code and Chinese State-owned Enterprises’ Freedom in Contracting: One Step Too Far
Authors: Jiang Hao , von Appen Antonia
Published: July 2022

Upon the enactment of Chinese Civil Code, the previous rules that allowed for enlarged state power to annul contracts such as General Principles of Civil Law article 58 §3 and Contract Law article 52 §1-§2 were dropped. Chinese law has gone one step further in promoting freedom of contract. The validity rules now have been streamlined and the previous contradictory and inconsistent treatment between civil juristic acts and contracts, state and private parties eliminated. However, the new legislative technique will unavoidably facilitate asset stripping, the very reason that the paternalistic rules were in place. Through a historical, doctrinal and logical lens, we will show why there can be no effective model of a neutral set of validity rules that could deal with state-owned enterprises in a less than free and competitive market. The only way to make it work is to have SOEs exit most of the competitive industries and focus on areas that serve the policy goals. Also, paternalistic rules concerning the validity of a contract in trading state-assets should be enacted either in the Civil Code or through special legislations and applicable to government, state-owned enterprises and private parties alike.
Early and late readmissions after enhanced recovery thoracoscopic lobectomy
Authors: Huang Lin , Frandsen Mikkel Nicklas , Kehlet Henrik , Petersen René Horsleben
Published: July 2022

OBJECTIVES

The purpose of this study was to describe the incidence of and reasons for early (0–30 days) and late (31–90 days) readmissions after enhanced recovery video-assisted thoracoscopic surgery lobectomy.

METHODS

We performed a retrospective analysis of prospectively collected consecutive VATS lobectomy data in an institutional database from January 2019 through December 2020. All reasons for readmission with complete follow-up were individually evaluated. Univariable and multivariable analyses were used to assess predictors.

RESULTS

In total, 508 patients were included; the median length of stay after the operation was 3 days. There were 77 (15%) early and 54 (11%) late readmissions, respectively. There were 33 (7%) multiple readmissions during postoperative days 0–90 ; pneumonia (19.8%) and pneumothorax (18.3%) were the dominant reasons for early readmissions, and the side effects of adjuvant chemotherapy (22.0%), for late readmissions. In multivariable analyses, current smoking (P = 0.001), alcohol abuse (P = 0.024) and chronic obstructive pulmonary disease (P = 0.019) were predictors of early readmissions, whereas Clavien-Dindo I-II grade gastrointestinal complications predicted late readmissions (P = 0.006) and multiple readmissions (P = 0.007). Early discharge (< 3 days) was not a predictor of readmissions. Early readmission did not increase late readmission.

CONCLUSIONS

Early and late readmissions after video-assisted thoracoscopic lobectomy are frequent even when enhanced recovery programmes are followed. Pulmonary complications and adjuvant chemotherapy are the most predominant reasons for early and late readmissions.
Analysis of transcriptome data and quantitative trait loci enables the identification of candidate genes responsible for fiber strength in Gossypium barbadense
Authors: Duan Yajie , Chen Qin , Chen Quanjia , Zheng Kai , Cai Yongsheng , Long Yilei , Zhao Jieyin , Guo Yaping , Sun Fenglei , Qu Yanying
Published: July 2022

Gossypium barbadense possesses a superior fiber quality because of its fiber length and strength. An in-depth analysis of the underlying genetic mechanism could aid in filling the gap in research regarding fiber strength and could provide helpful information for Gossypium barbadense breeding. Three quantitative trait loci related to fiber strength were identified from a Gossypium barbadense recombinant inbred line (PimaS-7 × 5917) for further analysis. RNA sequencing was performed in the fiber tissues of PimaS-7 × 5917 0–35 days postanthesis. Four specific modules closely related to the secondary wall-thickening stage were obtained using the weighted gene coexpression network analysis. In total, 55 genes were identified as differentially expressed from 4 specific modules. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes were used for enrichment analysis, and Gbar_D11G032910, Gbar_D08G020540, Gbar_D08G013370, Gbar_D11G033670, and Gbar_D11G029020 were found to regulate fiber strength by playing a role in the composition of structural constituents of cytoskeleton and microtubules during fiber development. Quantitative real-time PCR results confirmed the accuracy of the transcriptome data. This study provides a quick strategy for exploring candidate genes and provides new insights for improving fiber strength in cotton.
Phylogenomic Analyses of 2,786 Genes in 158 Lineages Support a Root of the Eukaryotic Tree of Life between Opisthokonts and All Other Lineages
Authors: Cerón-Romero Mario A , Fonseca Miguel M , de Oliveira Martins Leonardo , Posada David , Katz Laura A
Published: July 2022

Advances in phylogenomics and high-throughput sequencing have allowed the reconstruction of deep phylogenetic relationships in the evolution of eukaryotes. Yet, the root of the eukaryotic tree of life remains elusive. The most popular hypothesis in textbooks and reviews is a root between Unikonta (Opisthokonta + Amoebozoa) and Bikonta (all other eukaryotes), which emerged from analyses of a single-gene fusion. Subsequent, highly cited studies based on concatenation of genes supported this hypothesis with some variations or proposed a root within Excavata. However, concatenation of genes does not consider phylogenetically-informative events like gene duplications and losses. A recent study using gene tree parsimony (GTP) suggested the root lies between Opisthokonta and all other eukaryotes, but only including 59 taxa and 20 genes. Here we use GTP with a duplication-loss model in a gene-rich and taxon-rich dataset (i.e., 2,786 gene families from two sets of 155 and 158 diverse eukaryotic lineages) to assess the root, and we iterate each analysis 100 times to quantify tree space uncertainty. We also contrasted our results and discarded alternative hypotheses from the literature using GTP and the likelihood-based method SpeciesRax. Our estimates suggest a root between Fungi or Opisthokonta and all other eukaryotes; but based on further analysis of genome size, we propose that the root between Opisthokonta and all other eukaryotes is the most likely.
Chromosome-Scale Genome Assembly of the Hexaploid Taiwanese Goosefoot “Djulis” (Chenopodium formosanum)
Authors: Jarvis David E , Sproul John S , Navarro-Domínguez Beatriz , Krak Karol , Jaggi Kate , Huang Yung-Fen , Huang Tzu-Yun , Lin Tzu Che , Jellen Eric N , Maughan Peter J
Published: July 2022

Djulis (Chenopodium formosanum Koidz.) is a crop grown since antiquity in Taiwan. It is a BCD-genome hexaploid (2n = 6x = 54) domesticated form of lambsquarters (C. album L.) and a relative of the allotetraploid (AABB) C. quinoa. As with quinoa, djulis seed contains a complete protein profile and many nutritionally important vitamins and minerals. While still sold locally in Taiwanese markets, its traditional culinary uses are being lost as diets of younger generations change. Moreover, indigenous Taiwanese peoples who have long safeguarded djulis are losing their traditional farmlands. We used PacBio sequencing and Hi-C-based scaffolding to produce a chromosome-scale, reference-quality assembly of djulis. The final genome assembly spans 1.63 Gb in 798 scaffolds, with 97.8% of the sequence contained in 27 scaffolds representing the nine haploid chromosomes of each sub-genome of the species. Benchmarking of universal, single-copy orthologs indicated that 98.5% of the conserved orthologous genes for Viridiplantae are complete within the assembled genome, with 92.9% duplicated, as expected for a polyploid. A total of 67.8% of the assembly is repetitive, with the most common repeat being Gypsy long terminal repeat retrotransposons, which had significantly expanded in the B sub-genome. Gene annotation using Iso-Seq data from multiple tissues identified 75,056 putative gene models. Comparisons to quinoa showed strong patterns of synteny which allowed for the identification of homoeologous chromosomes, and sub-genome-specific sequences were used to assign homoeologs to each sub-genome. These results represent the first hexaploid genome assembly and the first assemblies of the C and D genomes of the Chenopodioideae subfamily.
Increasing Pain Interference Is Associated With Cognitive Decline Over Four Years Among Older Puerto Rican Adults
Authors: Milani Sadaf Arefi , Bell Tyler R , Crowe Michael , Pope Caitlin N , Downer Brian
Published: July 2022

Background

Pain is associated with cognitive decline among older adults, but few studies have investigated bidirectional associations between pain and cognitive decline, especially in older Hispanic populations. Our objective was to assess the bidirectional association between pain interference and cognitive performance in a sample of older Puerto Rican adults.

Methods

Data came from baseline and 4-year follow-up of the Puerto Rican Elderly: Health Conditions Study, a longitudinal representative study of Puerto Rican older adults aged 60 and older. Pain and cognitive performance were assessed at each wave. A pain interference variable was created using the sum of pain status (yes/no) and pain interference (yes/no; range 0–2). Global cognitive performance was assessed with the Mini-Mental Cabán. We tested bidirectional associations using a path model with concurrent and cross-lagged paths between pain and cognitive performance, adjusting for sociodemographic and health factors (n = 2 349).

Results

Baseline pain interference was not associated with baseline cognitive performance (p = .636) or with cognitive performance at follow-up (p = .594). However, increased pain interference at follow-up was associated with greater cognitive decline at follow-up (β = −0.07, standard error [SE] = 0.02, p = .003). Greater baseline cognitive performance was associated with lower pain interference at follow-up (β = −0.07, SE = 0.02, p = .007).

Conclusions

These findings highlight the importance of worsening pain interference as a potentially modifiable risk factor for cognitive decline, as pain treatment options exist. Additionally, better baseline cognitive performance may be a protective factor for pain, providing further evidence of the dynamic relationship between pain and cognitive performance.
Patient-Reported Barriers and Enablers to Deprescribing Recommendations During a Clinical Trial (Shed-MEDS)
Authors: Kim Jennifer L , Lewallen Kanah M , Hollingsworth Emily K , Shah Avantika S , Simmons Sandra F , Vasilevskis Eduard E
Published: July 2022

Background and Objectives

Effective deprescribing requires shared decision making between a patient and their clinician, and should be used when implementing evidence-based deprescribing conversations. As part of the Shed-MEDS clinical trial, this study assessed barriers and enablers that influence patient decision making in deprescribing to inform future implementation efforts and adaptations.

Research Design and Methods

Shed-MEDS, a randomized controlled deprescribing trial, included hospitalized older adults discharging to post-acute care facilities. A trained clinician reviewed each participant’s medical history and medication list to identify medications with potential for deprescribing. The study clinician then conducted a semistructured patient-centered deprescribing interview to determine patient (or surrogate) concerns about medications and willingness to deprescribe. Reeve et al.’s (2013) framework was used to categorize barriers and enablers to deprescribing from the patient’s perspective, including “appropriateness of cessation,” “fear,” “dislike of a medication,” “influences,” and “process of cessation.”

Results

Overall, participants/surrogates (N = 177) agreed with 63% (883 total medications) of the study clinician’s deprescribing recommendations. Thematic analysis revealed that “appropriateness” of a medication was the most common barrier (88.2%) and enabler (67.3%) to deprescribing. Other deprescribing enablers were in the following domains: “influences” (22.7%), “process” (22.5%), “pragmatic” (19.4%), and “dislike” (5.3%).

Discussion and Implications

Use of a semistructured deprescribing interview conversation tool allowed study clinicians to elicit individual barriers and enablers to deprescribing from the patient’s perspective. Participants in this study expressed more agreement than disagreement with study clinicians’ deprescribing recommendations. These results should inform future implementation efforts that incorporate a patient-centered framework during deprescribing conversations.

Clinical Trials Registration Number

NCT02979353
Saving Ukrainian Lives During the Russian War: Ukraine Must Waive IP Rights under Article 73 TRIPS to Provide Access to Essential Medicines
Authors: Gurgula Olga
Published: July 2022

In light of the severity of the health crisis in Ukraine due to the Russian aggression, the Ukrainian government must urgently implement expeditious solutions to increase the supply of essential medicines and medical products. One such measure is to exploit all existing domestic manufacturing capacities that are still intact and seek any potential possibility to import essential medicines from abroad. For this, all the barriers would need to be eliminated, including those in the form of intellectual property (IP) rights that might protect many essential medicines that are currently needed in Ukraine. This article argues that the existing mechanism of compulsory licensing under TRIPS and Ukrainian IP law is not effective to resolve the problem of access to medicines during such a critical situation as the ongoing war. It therefore suggests that Ukraine must immediately waive all IP rights related to essential medicines and medical products to enable the domestic production and seek any potential import of generics and biosimilars of essential medicines. Such a waiver would be justified based on ‘security exceptions’ of Art. 73(b)(iii) TRIPS. This provision allows a WTO member to utilise measures to protect its essential security interests taken in time of war. It is hoped that this article will provide guidance to the Ukrainian government on the most effective way to deal with the current health crisis in Ukraine and, thus, would help to save lives of millions of people in Ukraine that suffer from Russia’s unjustified, horrific aggression.
Increased Expression of Interleukin-13 Receptor in Ileum Associated With Nonresponse to Adalimumab in Ileal Crohn’s Disease
Authors: Wong Emily C L , Yusuf Arif , Pokryszka Jagoda , Dulai Parambir S , Colombel Jean-Frederic , Marshall John K , Reinisch Walter , Narula Neeraj
Published: July 2022

Background

The terminal ileum poses a predilection for Crohn’s disease (CD) but is less susceptible to undergo healing to treatment with biologics and small molecules. This study aimed to evaluate histologic features associated with endoscopic remission (ER).

Methods

This is a post hoc analysis of patients with moderately to severely active CD, defined as Crohn’s disease activity index 220 to 450, and terminal ileal ulceration treated with antitumor necrosis factor (TNF)-α inhibitor adalimumab from the EXTEND trial. We studied whether baseline total Global Histologic Disease Activity Scores (GHAS), any individual histologic element, and specific immunohistochemical (IHC) markers of chronic inflammation from biopsy specimens were associated with postinduction (week 12) and maintenance (week 52) ER, defined as Simple Endoscopic Score for Crohn’s Disease of 0. Multivariable logistic regression models adjusted for confounders were used to assess the relationship between histologic markers and 1-year outcomes.

Results

Seventy-one adult patients with CD affecting the ileum were included in this analysis. Both baseline ileal GHAS scores and individual histologic components were not found to be associated with ER at weeks 12 or 52. Increased expression of interleukin-13 receptor (IL-13R) on IHC stains was associated with reduced likelihood of achieving 1-year ER (adjusted odds ratio, 0.06; 95% CI, 0.01-0.92; P = .044). No other biomarker assessed was associated with 1-year ER.

Conclusions

Ileal histologic disease activity and IHC activation markers of chronic mucosal inflammation were not associated with 1-year ER. However, strong staining for IL-13 receptor in the ileum was associated with reduced odds of 1-year ER using adalimumab. Mucosal cellular disease profiles might pose an opportunity to guide treatment of CD.
5-HT5A Receptor Antagonist ASP5736 Ameliorates Several Abnormal Behaviors in an Fmr1-Targeted Transgenic Male Rat Model of Fragile X Syndrome
Authors: Yamazaki Mayako , Arai Takatomo , Yarimizu Junko , Matsumoto Mitsuyuki
Published: July 2022

Background

Fragile X syndrome (FXS) is a genetic condition that causes a range of developmental problems, including intellectual disability, aggressive behavior, anxiety, abnormal sensory processing, and cognitive impairment. Despite intensive preclinical research in Fmr1-targeted transgenic mice, an effective treatment for FXS has yet to be developed. We previously demonstrated that ASP5736, a 5-Hydroxytryptamine (serotonin) receptor 5A receptor antagonist, ameliorated scopolamine-induced working memory deficits in mice, reference memory impairment in aged rats, and methamphetamine-induced positive symptoms and phencyclidine-induced cognitive impairment in animal models of schizophrenia. We hypothesized that ASP5736 may be effective for ameliorating similar behavior deficits in male Fmr1-targeted transgenic rats as a preclinical model of FXS.

Methods

We evaluated the effect of acute oral administration of ASP5736 on the abnormal behavior of hyperactivity (0.01, 0.1 mg/kg), prepulse inhibition (0.01, 0.03, 0.1 mg/kg), and the novel object recognition task (0.1 mg/kg) in Frmr1-knockout (KO) rats.

Results

Fmr1-KO rats showed body weight gain, hyperactivity, abnormal sensory motor gating, and cognitive impairment. ASP5736 (0.1 mg/kg) reversed the hyperactivity and ameliorated the sensory motor gating deficits (0.03–0.1 mg/kg). ASP5736 (0.01 mg/kg) also improved cognitive impairment.

Conclusions

ASP5736 is a potential drug candidate for FXS. Further studies are needed to confirm its clinical efficacy.
Zelquistinel Is an Orally Bioavailable Novel NMDA Receptor Allosteric Modulator That Exhibits Rapid and Sustained Antidepressant-Like Effects
Authors: Burgdorf Jeffrey S , Zhang Xiao-Lei , Stanton Patric K , Moskal Joseph R , Donello John E
Published: July 2022

Background

The role of glutamatergic receptors in major depressive disorder continues to be of great interest for therapeutic development. Recent studies suggest that both negative and positive modulation of N-methyl-D-aspartate receptors (NMDAR) can produce rapid antidepressant effects. Here we report that zelquistinel, a novel NMDAR allosteric modulator, exhibits high oral bioavailability and dose-proportional exposures in plasma and the central nervous system and produces rapid and sustained antidepressant-like effects in rodents by enhancing activity-dependent, long-term synaptic plasticity.

Methods

NMDAR-mediated functional activity was measured in cultured rat brain cortical neurons (calcium imaging), hNR2A or B subtype-expressing HEK cells, and synaptic plasticity in rat hippocampal and medial prefrontal cortex slices in vitro. Pharmacokinetics were evaluated in rats following oral administration. Antidepressant-like effects were assessed in the rat forced swim test and the chronic social deficit mouse model. Target engagement and the safety/tolerability profile was assessed using phencyclidine-induced hyperlocomotion and rotarod rodent models.

Results

Following a single oral dose, zelquistinel (0.1–100 µg/kg) produced rapid and sustained antidepressant-like effects in the rodent depression models. Brain/ cerebrospinal fluid concentrations associated with zelquistinel antidepressant-like activity also increased NMDAR function and rapidly and persistently enhanced activity-dependent synaptic plasticity (long-term potentiation), suggesting that zelquistinel produces antidepressant-like effects by enhancing NMDAR function and synaptic plasticity. Furthermore, Zelquistinel inhibited phencyclidine (an NMDAR antagonist)-induced hyperlocomotion and did not impact rotarod performance.

Conclusions

Zelquistinel produces rapid and sustained antidepressant effects by positively modulating the NMDARs, thereby enhancing long-term potentiation of synaptic transmission.
Asymptotic solutions of the SIR and SEIR models well above the epidemic threshold
Authors: Kozyreff Gregory
Published: July 2022

A simple and explicit expression of the solution of the SIR epidemiological model of Kermack and McKendrick is constructed in the asymptotic limit of large basic reproduction numbers ${\mathsf R_0}$. The proposed formula yields good qualitative agreement already when ${\mathsf R_0}\geq 3$ and rapidly becomes quantitatively accurate as larger values of ${\mathsf R_0}$ are assumed. The derivation is based on the method of matched asymptotic expansions, which exploits the fact that the exponential growing phase and the eventual recession of the outbreak occur on distinct time scales. From the newly derived solution, an analytical estimate of the time separating the first inflexion point of the epidemic curve from the peak of infections is given. Finally, we use the same method on the SEIR model and find that the inclusion of the ‘exposed’ population in the model can dramatically alter the time scales of the outbreak.
Framework for integrating electronic patient-reported data in routine cancer care: an Oncology Intake Questionnaire
Authors: McCleary Nadine J , Haakenstad Ellana K , Cleveland Jessica L F , Manni Michael , Hassett Michael J , Schrag Deb
Published: July 2022

Objective

As part of ongoing implementation of electronic patient-reported outcome tools at the Dana-Farber Cancer Institute, here we describe the development of the electronic New Patient Intake Questionnaire.

Materials and Methods

The original New Patient Intake Questionnaire includes a review of symptoms, oncology history, family history, health behaviors, health and social status, health literacy and numeracy, which was modified for integration into the EHR using content determination, build and configuration, implementation, analytics, and interventions. The engagement of key stakeholders, including patients, clinical staff, and providers, throughout the development and deployment of the electronic Questionnaire was crucial to producing a successful tool. Continual modifications based on input of stakeholders (such as mode of tool deployment) were made to ensure the utility and usability of the tool for both patients and providers.

Results

Implementation of the EHR-integrated electronic New Patient Intake Questionnaire improved collection of the PRD by increasing questionnaire accessibility for patients, while also providing all available data to clinicians and researchers. Careful consideration of the content and configuration of the questionnaire allowed for a successful, institute-wide implementation of the tool.

Discussion

This effort demonstrates the feasibility of implementation of a system-wide electronic questionnaire, emphasizing the importance of iterative refinement to create a tool that is both patient-centric and usable for clinicians.

Conclusions

The electronic New Patient Intake Questionnaire allows for systematic collection of the PRD, which should benefit cancer care outcomes through innovative care delivery and healthcare interventions.
Sanitizing Equipment and Personnel to Prevent the Spread of Hibiscus Mealybug [Nipaecoccus viridis (Hemiptera: Pseudococcidae)] in Florida Citrus
Authors: Middleton Eric G , Diepenbrock Lauren M
Published: July 2022

Hibiscus mealybug (Nipaecoccus viridis, Newstead) is an emerging and serious pest of citrus in Florida. Preventing the spread of hibiscus mealybug by sanitizing personnel and equipment such as individual protective covers can help limit new infestations. Two mealybug life stages, first instars (crawlers) and eggs inside ovisacs, were tested as they are the most likely to be accidentally transported on people and tools. Isopropanol sprays in 3 commercially available concentrations (50%, 70%, and 90%) were tested against crawlers and ovisacs, and steam treatments and hot water immersion were tested against ovisacs. All concentrations of isopropanol resulted in >90% incapacitation of mealybug crawlers, especially when two sprays of isopropanol were applied. However, no concentration of isopropanol reliably killed all mealybug eggs within ovisacs. Steam treatments and hot water immersion for 10 min or longer at 49°C and for 5 min or longer at 54.5°C resulted in 100% mortality of mealybug adults and eggs inside ovisacs. However, adults and ovisacs insulated inside of individual protective covers did not experience 100% mortality until 30 min or longer at 49°C, 10 min or longer at 54.5°C, and 5 min or longer at 60°C for steam treatments. Isopropanol sprays can effectively incapacitate the majority of hibiscus mealybug crawlers on personnel and tools, but are not effective against ovisacs. Steam treatments and hot water immersion can reliably lead to 100% mortality of ovisacs, but longer times and higher temperatures must be used for steam treatments if ovisacs are insulated by equipment.
New Identification Tools for the Nymphs of Three Amblyomma spp. Koch (Ixodida: Ixodidae) in South Texas
Authors: Alfred J T , Mertins J W
Published: July 2022

Taxonomic uncertainties and morphologic and molecular similarities may lead to incorrect or incomplete species identifications of immature ticks. This problem can be compounded when the diagnostic morphological features used are unreliable, unstable, or difficult to view. Our study attempts to sort out the similar morphologies of three Amblyomma spp. nymphs with partially overlapping geographic distributions in South Texas. Amblyomma americanum (L.), Amblyomma mixtum Koch, and Amblyomma tenellum Koch are three closely related species with similar nymphs and larvae. Previous attempts to morphologically distinguish among nymphs of these species have relied on difficult-to-observe and unreliable characters. Over the course of decades of routine diagnostic work with these ticks, we have observed and discovered consistent and useful morphologic features sufficient to practically distinguish among these nymphs. We confirmed our morphological studies with molecular genetic evidence (i.e., 12S mitochondrial genes), and we propose that practical, rapid morphological species-level identification of nymphs of the three named species is now possible with confidence.
MTH-3 sensitizes oral cancer cells to cisplatin via regulating TFEB
Authors: Tsai Shih-Chang , Yang Jai-Sing , Lu Chi‑Cheng , Tsai Fuu-Jen , Chiu Yu‑Jen , Kuo Sheng-Chu
Published: July 2022

Objectives

MTH-3, a curcumin derivative, exhibits improved water solubility. This study aims to elucidate the mechanisms underlying the anticancer effects of MTH-3 on human oral squamous cell carcinoma CAL27 cisplatin-resistant (CAR) cells.

Methods

To evaluate the biological functions of MTH-3 in CAR cells, flow cytometry, staining, and western blot analyses were used.

Key findings

MTH-3 reduced CAR cell viability and significantly induced autophagy in the presence of 10 and 20 μM MTH-3. Transcription factor EB was identified as the potential target of MTH-3. Autophagy-related proteins were upregulated after 24 h of MTH-3 incubation. MTH-3 treatment increased caspase-3 and caspase-9 enzyme activities. Mitochondrial membrane potential was decreased after MTH-3 treatment. MTH-3 triggered the intrinsic apoptotic pathway.

Conclusions

MTH-3 induces autophagy and apoptosis of CAR cells via TFEB. MTH-3 might be an effective pharmacological agent for treating oral cancer cells.
Military Resident Physician Training Burden: Quantifying Requirements Across the Military Health Care System
Authors: Medvescek Eli D , Foglia Lisa M , Thagard Andrew S
Published: July 2022

Introduction

The Military Health Care System trains approximately 1,500 resident physicians in over 100 specialties. In addition to requirements for their specific program, active duty military trainees must complete military-specific trainings that vary by the branch of service. Excessive training requirements could contribute to physician burnout and/or negatively affect patient care. Therefore, the objective of this study was to quantify the time active duty resident physicians dedicate to this training, stratified by the branch of service.

Materials and Methods

The study protocol was submitted to the Clinical Investigations Department at Naval Medical Center Portsmouth (Portsmouth, VA, USA) and deemed exempt from the Institutional Review Board review. We conducted a descriptive study in 2021 wherein lists of all training requirements were obtained from a military treatment facility in the Army, Navy, and Air Force supporting residency training. Individual requirements were reviewed and sorted into military-specific and general categories. Information was gathered on duration, frequency, and platform for applicable requirements.

Results

Residents are required to complete a mean of 17.2 hours of training annually, of which 11.2 hours were military-specific. This consisted of 50, 57, and 53 individual requirements for Army, Navy, and Air Force personnel, respectively. Army resident physicians had the greatest time burden of military-specific training at 14.8 hours/year, followed by the Air Force and Navy (10.2 and 8.7 hours/year, respectively).

Conclusions

Annually, active duty resident physicians spend the equivalent of more than two work days completing additional training requirements on multiple platforms. Standardizing training requirements and platforms across the Military Health Care System and aligning required trainings with job responsibilities could free up additional time for patient care, potentially decreasing fatigue and burnout.
The positive evidence bias in perceptual confidence is unlikely post-decisional
Authors: Samaha Jason , Denison Rachel
Published: July 2022

Confidence in a perceptual decision is a subjective estimate of the accuracy of one’s choice. As such, confidence is thought to be an important computation for a variety of cognitive and perceptual processes, and it features heavily in theorizing about conscious access to perceptual states. Recent experiments have revealed a “positive evidence bias” (PEB) in the computations underlying confidence reports. A PEB occurs when confidence, unlike objective choice, overweights the evidence for the correct (or chosen) option, relative to evidence against the correct (or chosen) option. Accordingly, in a perceptual task, appropriate stimulus conditions can be arranged that produce selective changes in confidence reports but no changes in accuracy. Although the PEB is generally assumed to reflect the observer’s perceptual and/or decision processes, post-decisional accounts have not been ruled out. We therefore asked whether the PEB persisted under novel conditions that addressed two possible post-decisional accounts: (i) post-decision evidence accumulation that contributes to a confidence report solicited after the perceptual choice and (ii) a memory bias that emerges in the delay between the stimulus offset and the confidence report. We found that even when the stimulus remained on the screen until observers responded, and when observers reported their choice and confidence simultaneously, the PEB still emerged. Signal detection-based modeling showed that the PEB was not associated with changes to metacognitive efficiency, but rather to confidence criteria. The data show that memory biases cannot explain the PEB and provide evidence against a post-decision evidence accumulation account, bolstering the idea that the PEB is perceptual or decisional in nature.
Real-time PACS-integrated longitudinal brain metastasis tracking tool provides comprehensive assessment of treatment response to radiosurgery
Authors: Cassinelli Petersen Gabriel , Bousabarah Khaled , Verma Tej , von Reppert Marc , Jekel Leon , Gordem Ayyuce , Jang Benjamin , Merkaj Sara , Abi Fadel Sandra , Owens Randy , Omuro Antonio , Chiang Veronica , Ikuta Ichiro , Lin MingDe , Aboian Mariam S
Published: July 2022

Background

Treatment of brain metastases can be tailored to individual lesions with treatments such as stereotactic radiosurgery. Accurate surveillance of lesions is a prerequisite but challenging in patients with multiple lesions and prior imaging studies, in a process that is laborious and time consuming. We aimed to longitudinally track several lesions using a PACS-integrated lesion tracking tool (LTT) to evaluate the efficiency of a PACS-integrated lesion tracking workflow, and characterize the prevalence of heterogenous response (HeR) to treatment after Gamma Knife (GK).

Methods

We selected a group of brain metastases patients treated with GK at our institution. We used a PACS-integrated LTT to track the treatment response of each lesion after first GK intervention to maximally seven diagnostic follow-up scans. We evaluated the efficiency of this tool by comparing the number of clicks necessary to complete this task with and without the tool and examined the prevalence of HeR in treatment.

Results

A cohort of eighty patients was selected and 494 lesions were measured and tracked longitudinally for a mean follow-up time of 374 days after first GK. Use of LTT significantly decreased number of necessary clicks. 81.7% of patients had HeR to treatment at the end of follow-up. The prevalence increased with increasing number of lesions.

Conclusions

Lesions in a single patient often differ in their response to treatment, highlighting the importance of individual lesion size assessments for further treatment planning. PACS-integrated lesion tracking enables efficient lesion surveillance workflow and specific and objective result reports to treating clinicians.
Dynamic confinement of SAPO-17 cages on the selectivity control of syngas conversion
Authors: Wang Haodi , Jiao Feng , Ding Yi , Liu Wenjuan , Xu Zhaochao , Pan Xiulian , Bao Xinhe
Published: July 2022

The OXZEO (oxide−zeolite) bifunctional catalyst concept has enabled selective syngas conversion to a series of value-added chemicals and fuels such as light olefins, aromatics and gasoline. Herein we report for the first time a dynamic confinement of SAPO-17 cages on the selectivity control of syngas conversion observed during an induction period. Structured illumination microscopy, intelligent gravimetric analysis, UV-Raman, X-ray diffraction, thermogravimetry and gas chromatography-mass spectrometer analysis indicate that this is attributed to the evolution of carbonaceous species as the reaction proceeds, which gradually reduces the effective space inside the cage. Consequently, the diffusion of molecules is hindered and the hindering is much more prominent for larger molecules such as C4+. As a result, the selectivity of ethylene is enhanced whereas that of C4+ is suppressed. Beyond the induction period, the product selectivity levels off. For instance, ethylene selectivity levels off at 44% and propylene selectivity at 31%, as well as CO conversion at 27%. The findings here bring a new fundamental understanding that will guide further development of selective catalysts for olefin synthesis based on the OXZEO concept.
Epidemiology and Factors Associated With Discharging Patients After Blood Culture Collection in the Emergency Department: A Case-Control Study in Japan
Authors: Miwa Toshiki , Takamatsu Akane , Honda Hitoshi
Published: July 2022

Background

Some patients receive the diagnosis of bloodstream infection (BSI) after discharge from the emergency room (ER). Because the safety of discharging patients after a blood culture collection is unknown, the present study aimed to investigate the prevalence, outcomes, and factors associated with BSI diagnosed after ER discharge.

Methods

This monocentric, case-control study compared patients who received a BSI diagnosis after ER discharge with those who were admitted for BSI. Factors associated with ER discharge after a blood culture collection were identified using multivariate logistic regression analysis.

Results

Between January 2014 and December 2020, 5.5% (142/2575) of patients with BSI visiting the ER were initially discharged. This occurred more commonly during the coronavirus disease 2019 (COVID-19) pandemic in 2020. On multivariate analysis, factors independently associated with the discharge of patients with BSI were the absence of hypotension (adjusted odds ratio [aOR], 15.71 [95% confidence interval {CI}, 3.45–71.63]), absence of altered mental status in the ER (aOR, 8.99 [95% CI, 3.49–23.14]), unknown origin at ER discharge (aOR, 4.60 [95% CI, 2.43–8.72]), and low C-reactive protein (aOR, 3.60 [95% CI, 2.19–5.93]). No difference in 28-day mortality was observed between the groups.

Conclusions

BSI is occasionally diagnosed after ER discharge. The prevalence of BSI diagnosed after ER discharge may have increased during the COVID-19 pandemic. Normal vital signs, unknown origin at ER discharge, and low C-reactive protein were important considerations leading to the discharge of these patients.
Sensitivity of the Elecsys Nucleocapsid Assay for the Detection of Preceding SARS-CoV-2 Infections
Authors: Grunau Brian , Tom Janessa , Asamoah-Boaheng Michael , O’Brien Sheila F , Drews Steven J , Sediqi Sadaf , Lavoie Pascal M , Barakauskas Vilte , Goldfarb David M
Published: July 2022

Nucleocapsid serological assay sensitivity to identify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections among vaccinees and for Omicron cases is unclear. In this prospective study, the Elecsys nucleocapsid assay was 89% sensitive in identifying SARS-CoV-2 infections 14–607 days pre–blood collection. Sensitivity was similar when comparing by vaccination status, and in Omicron (vs pre-Omicron) cases.
Clinical Features and Treatment Outcomes of Pulmonary Mycobacterium avium-intracellulare Complex With and Without Coinfections
Authors: Wang Grace , Stapleton Jack T , Baker Arthur W , Rouphael Nadine , Creech C Buddy , El Sahly Hana M , Stout Jason E , Jackson Lisa , Charbek Edward , Leyva Francisco J , Tomashek Kay M , Tibbals Melinda , Miller Aaron , Frey Sharon , Niemotka Samson , Wiemken Timothy L , Beydoun Nour , Alaaeddine Ghina , Turner Nicholas , Walter Emmanuel B , Chamberland Robin , Abate Getahun
Published: July 2022

Coinfections are more common in patients with cystic fibrosis and bronchiectasis. Infiltrates on imaging studies are seen more commonly in patients with coinfections, but coinfections did not affect treatment outcomes of pulmonary Mycobacterium avium complex.
Thoraco-abdominal duplication cyst of the jejunum presenting as respiratory distress in a young infant—a case report
Authors: Harputluoğlu Nilgün , Çelik Tanju , Temir Günyüz , Hoşgör Münevver
Published: July 2022

Thoraco-abdominal duplication cysts are rare congenital anomalies that can accompany vertebral and spinal cord pathologies and occur most frequently in the small intestines. Symptoms such as respiratory distress, dyspnea, tachypnea, cough, hemoptysis, cyanosis, vomiting and dysphagia may develop depending on the location. The cyst has several clinical and radiological dilemmas. We present a rare case of thoraco-abdominal duplication cyst in a 3-month-old male patient presenting with respiratory distress in the neonatal period. Thoraco-abdominal duplications require a high index of suspicion and meticulous clinical management. Thus, patients can be successfully managed without any unnecessary interventions, complications and loss of time.
Extensive aortic thrombosis and testicular infarction – a rare complication of biventricular cardiac thrombi
Authors: Ezad Saad M , Salmon Andrew , Cheema Hooria , Swallow Rosie
Published: July 2022

Heart failure is a heterogenous syndrome which is increasing in prevalence, with a prognosis worse than many malignancies. Morbidity and mortality most commonly occur secondary to pump failure or ventricular arrhythmias; however, a more infrequently seen complication is the formation of mural thrombi. More commonly seen within the left ventricle, thrombi can embolize leading to stroke or end organ infarction. We present the case of a male who presented with decompensated heart failure. The presence of biventricular thrombi was found on echocardiography and subsequent cross-sectional imaging revealed these had embolized resulting in the rare complication of extensive abdominal aortic thrombosis with renal and testicular infarction. Biventricular thrombi are rare but high risk due to the potential for embolization as demonstrated in this case. Prompt recognition and management with anti-coagulation are essential, followed by treatment of the underlying pathology, which resulted in the formation of thrombi to prevent recurrence.
Emergency surgical decompression and long-term survival of glioblastoma presenting in coma in old age: case report and review of prognostic factors
Authors: McKinley Aidan , Lammy Simon , James Allan , Stan Alexandru , Barrett Chris
Published: July 2022

We present a case demonstrating that older age does not exclude long-term survival with glioblastoma. This is a malignant neoplasm with a median life expectancy of 14 months in patients treated with radical intent. Survival is dependent on several independent and interacting prognostic factors of which advancing age is a negative factor. We present a septuagenarian with a 3.5-year survival following aggressive management. The potential to improve glioblastoma survival in an elderly population by examination of additional prognostic factors and identifying biomarkers warrants further research.
Subglottic mucormycosis in a COVID-19 patient: a rare case report
Authors: Amirzargar Behrooz , Jafari Mehrdad , Ahmadinejad Zahra , Salehi Mohammadreza , Chalabi Sina , Aminishakib Pouyan , Salahshoor Faeze , Khodavaisy Sadegh , Zabihidan Mohammadsadegh
Published: July 2022

Mucormycosis is an opportunistic fungal infection caused by fungi of Mucorale order. Uncontrolled diabetes mellitus and other immunosuppressive conditions such as neutropenia and corticosteroid therapy are known risk factors. A new risk factor for this infection is COVID-19 which facilitates mucormycosis by different mechanisms. The rhino-orbito-cerebral involvement is the most common form. Involvement of other anatomical regions may occur in rare situations. As we presented here, a 51-year-old woman presented with respiratory distress and subglottic lesion during COVID-19 (Delta variant) treatment which was diagnosed by histopathological examination as a subglottic mucormycosis postoperatively. The patient underwent tracheostomy and debridement of the necrotic tissues followed by antifungal treatment. New manifestations of COVID-19 are appearing over time. The association between coronavirus and mucormycosis of the laryngeal and airway region must be given serious consideration. Current guidelines recommend a combined medical and surgical approach for achieving the best outcome.