bluuebunny/crossref_metadata_2025 huggingface dataset:
Segmentation Errors in the Measurement of Volumetric Parameters by Swept-Source Anterior Segment Optical Coherence Tomography
Authors: Chen Hailiu , Meng Jie , Lu Peng , Ye Dan , Li Yunxuan , Cheng Lu , Li Yangyunhui , Liang Xiaoling , Huang Wenyong , Huang Jingjing
Published: December 2021

Purpose: To investigate the error rate of segmentation in the automatic measurement of anterior chamber volume (ACV) and iris volume (IV) by swept-source anterior segment optical coherence tomography (SS-ASOCT) in narrow-angle and wide-angle eyes.

Methods: In this study, fifty eyes from 25 narrow-angle subjects and fifty eyes from 25 wide-angle subjects were enrolled. SS-ASOCT examinations were performed and each SS-ASOCT scan was reviewed, and segmentation errors in the automatic measurement of ACV and IV were classified and manually corrected. Error rates were compared between the narrow-angle and the wide-angle groups, and ACV and IV before and after manual correction were compared.

Results: A total of 12,800 SS-ASOCT scans were reviewed. Segmentation error rates of angle recess, iris root, posterior surface of the iris, pupil margin, and anterior surface of the lens were 84.06, 93.30, 13.15, 59.21, and 25.27%, respectively. Segmentation errors of angle recess, iris root, posterior surface of the iris, and pupil margin occurred more frequently in narrow-angle eyes, while more segmentation errors of the anterior surface of the lens were found in wide-angle eyes (all P < 0.001). ACV decreased and IV increased significantly after manual correction of segmentation errors in both groups (all P < 0.01).

Conclusion: Segmentation errors were prevalent in the volumetric measurement by SS-ASOCT, particularly in narrow-angle eyes, leading to mismeasurement of ACV and IV.
Long-Term Outcomes of IgG4-Related Ophthalmic Disease in a Chinese IgG4-Related Disease Cohort
Authors: Gan Linyang , Luo Xuan , Fei Yunyun , Peng Linyi , Zhou Jiaxin , Li Jieqiong , Lu Hui , Liu Zheng , Zhang Panpan , Liu Xiaowei , Zhang Wen
Published: December 2021

Purpose: To define the treatment response and long-term outcomes of a large IgG4-related ophthalmic disease (IgG4-ROD) cohort.

Methods: A total of 132 patients with a minimum follow-up of 1 year were included in this study. Demographic, clinical, and laboratory data were collected. Treatment response was assessed by the IgG4-RD responder index (IgG4-RD RI). Risk factors for relapse were analyzed with the multivariate Cox regression analysis.

Results: The median follow-up time was 39 months. Lacrimal gland involvement was detected in 87.9% of cases. Extraocular muscles, the trigeminal nerve, and other soft tissue were affected in 25.8, 6.1, and 18.2% of patients. The relapse rate of watchful waiting, glucocorticoid monotherapy, immunosuppressant monotherapy, and combination therapy was 50.0, 51.7, 50.0, and 26.7% (p = 0.038), respectively. The combination therapy group exhibited shorter glucocorticoids therapy duration (36 vs. 48 months, p = 0.009) and maintenance period (24 vs. 42 months, p = 0.003). At the 6th month, the median IgG4-RD RI declined from 12 to 1 and 105 (79.5%) patients achieved complete response (CR). Relapse occurred in 49 (37.1%) patients. The multivariate Cox regression analysis exhibited that CR at the 6th month was an independent protective factor for relapse. Patients with multiple ocular lesions suffered from a higher risk of relapse. No patient had severe adverse reactions to the treatment in this study.

Conclusion: Relapse was common in patients with IgG4-ROD. Patients receiving combination therapy showed a lower relapse rate and a shorter glucocorticoids therapy period. The presence of multiple ocular lesions was associated with a higher risk of relapse. CR at the 6th month might be a predictor for a better prognosis in IgG4-ROD. Thus, a more aggressive regimen should be prescribed for patients with a poor initial response.
Machine Retrograde Perfusion of Deceased Donor Kidneys: A Prospective Study
Authors: Zeng Jun , Jia ZiHao , Lin Tao , Song TuRun
Published: December 2021

Objective: To maximize the utilization of potential kidneys, improving perfusion and preservation techniques is necessary.

Methods: We investigated the safety and efficacy of retrograde machine perfusion of kidneys from deceased donors. A total of 30 kidneys were included and all the grafts were preserved in the Kidney Transporter machines. A total of 15 kidneys that received retrograde perfusion (RP) were selected as the RP group (n = 15) and their counterparts received standard antegrade perfusion (AP) as the control group (n = 15).

Results: All the recipients were followed up for 6 months. Renal resistance in the RP group remained stable during the perfusion. There was no primary nonfunction. No difference in the incidence of delayed graft function was found in both groups (3 in RP vs. 2 in AP, p = 0.62). The RP group had lower serum creatinine (RP vs. AP, 102.20 vs. 138.67, p = 0.05) and blood urea nitrogen (RP vs. AP, 6.44 vs. 8.71, p = 0.05) than that in the AP group at 6 months. Both the groups had comparable estimated glomerular filtration rate and cystatin C within 6 months.

Conclusion: This novel technique may be an effective and safe alternative for kidney preservation.
Diversity and Function of Wolf Spider Gut Microbiota Revealed by Shotgun Metagenomics
Authors: Wu Runbiao , Wang Luyu , Xie Jianping , Zhang Zhisheng
Published: December 2021

Wolf spiders (Lycosidae) are crucial component of integrated pest management programs and the characteristics of their gut microbiota are known to play important roles in improving fitness and survival of the host. However, there are only few studies of the gut microbiota among closely related species of wolf spider. Whether wolf spiders gut microbiota vary with habitats remains unknown. Here, we used shotgun metagenomic sequencing to compare the gut microbiota of two wolf spider species, Pardosa agraria and P. laura from farmland and woodland ecosystems, respectively. The results show that the gut microbiota of Pardosa spiders is similar in richness and abundance. Approximately 27.3% of the gut microbiota of P. agraria comprises Proteobacteria, and approximately 34.4% of the gut microbiota of P. laura comprises Firmicutes. We assembled microbial genomes and found that the gut microbiota of P. laura are enriched in genes for carbohydrate metabolism. In contrast, those of P. agraria showed a higher proportion of genes encoding acetyltransferase, an enzyme involved in resistance to antibiotics. We reconstructed three high-quality and species-level microbial genomes: Vulcaniibacterium thermophilum, Anoxybacillus flavithermus and an unknown bacterium belonging to the family Simkaniaceae. Our results contribute to an understanding of the diversity and function of gut microbiota in closely related spiders.
A Rapid Screening Method of Candidate Probiotics for Inflammatory Bowel Diseases and the Anti-inflammatory Effect of the Selected Strain Bacillus smithii XY1
Authors: Huang Xuedi , Ai Fang , Ji Chen , Tu Pengcheng , Gao Yufang , Wu Yalan , Yan Fujie , Yu Ting
Published: December 2021

Inflammatory bowel disease (IBD) is a chronic intestinal disease associated with the inflammatory gastrointestinal tract and microbiome dysbiosis. Probiotics are a promising intervention, and several probiotics have been reported to positively affect IBD remission and prevention, particularly on ulcerative colitis (UC). However, there is still a limitation in the knowledge of effectiveness and safety of probiotics therapies for IBD. Exploring more potential probiotics helps to find extensive evidence for probiotic intervention. This study established a rapid method for probiotics candidate screening and finally screened out one strain with the best protective effect. Forty strains isolated from four different sources were used for this screening. Hemolysis tests and acute toxic test evaluated strain safety. Zebrafish were first treated with dextran sodium sulfate (DSS) for colitis induction, and every bacteria were individually added to the fish water subsequently. Results showed eight strains could lower the larvae mortality within 3 days under a 0.6% DSS concentration, including Lacticaseibacillus rhamnosus GG, L. rhamnosus NBRC3425, Bacillus smithii DSM4216, B. smithii XY1, Bacillus coagulans NBRC12583, Bacillus coagulans XY2, Lactobacillus parafarraginis XYRR2, and Bacillus licheniformis XYT3. Among eight, B. smithii XY1 was the only strain having the equal ability to alleviate neutrophil infiltration in the larvae intestine with that ability of prednisolone under a 0.5% DSS concentration. Bacillus smithii XY1 restored intestinal epithelial cell integrity after DSS damage, as well as regulated the gene expression inflammation-related factors, indicating its bio-function of inflammatory response alleviation.
Clonal Dissemination of Clinical Carbapenem-Resistant Klebsiella pneumoniae Isolates Carrying fosA3 and blaKPC–2 Coharboring Plasmids in Shandong, China
Authors: Hao Yingying , Zhao Xuguang , Zhang Cui , Bai Yuanyuan , Song Zhen , Lu Xinglun , Chen Ran , Zhu Yaoyao , Wang Yueling
Published: December 2021

Treatment strategies of infection by carbapenem-resistant Klebsiella pneumoniae (CRKP) are limited. Fosfomycin, a broad-spectrum antibiotic, has attracted renewed interest in combination therapy to fight K. pneumoniae infections. However, reports on fosfomycin-resistant K. pneumoniae are increasing. Among the 57 CRKP strains, 40 (70.2%) were resistant to fosfomycin. Thus, whole-genome sequencing and bioinformatics analysis were conducted to reveal molecular characteristics of fosfomycin-resistant K. pneumoniae. Twenty-three isolates coharbored fosAkp and fosA3, with K. pneumoniae carbapenemase (KPC)-producing ST11-KL64-wzi64-O2 (n = 13) and ST11-KL47-wzi209-OL101 (n = 8), the predominating clonal groups, while fosA3 was not detected in isolates carrying class B carbapenemase genes. Twenty-two (out of 26) ST11-KL64 strains were positive for rmpA2, of which 12 carried fosA3. Four of the 23 fosA3-positive isolates could successfully transfer their fosfomycin-resistant determinants to Escherichia coli J53AziR. All four strains belonged to ST11-KL47 with the same pulsed-field gel electrophoresis profile, and their transconjugants acquired fosfomycin, carbapenem, and aminoglycoside resistance. A 127-kb conjugative pCT-KPC-like hybrid plasmid (pJNKPN52_KPC_fosA) coharboring fosA3, blaKPC–2, blaCTX–M–65, blaSHV–12, rmtB, and blaTEM–1 was identified. ST11-KL64 and ST11-KL47 K. pneumoniae, with higher resistance and virulence, should be critically monitored to prevent the future dissemination of resistance.
Stationary Lactococcus cremoris: Energetic State, Protein Synthesis Without Nitrogen and Their Effect on Survival
Authors: Douwenga Sieze , van Tatenhove-Pel Rinke J. , Zwering Emile , Bachmann Herwig
Published: December 2021

During storage and ripening of fermented foods, Lactococcus cremoris is predominantly in a non-growing state. L. cremoris can become stationary due to starvation or acidification, and its metabolism in these non-growing states affects the fermented product. Available studies on the response of L. cremoris to acid and starvation stress are based on population level data. We here characterized the energetic state and the protein synthesis capacity of stationary L. cremoris cultures at the single cell level. We show that glucose starved stationary cells are energy-depleted, while acid-induced stationary cells are energized and can maintain a pH gradient over their membrane. In the absence of glucose and arginine, a small pH gradient can still be maintained. Subpopulations of stationary cells can synthesize protein without a nitrogen source, and the subpopulation size decreases with increasing stationary phase length. Protein synthesis capacity during starvation only benefits culturability after 6 days. These results highlight significant differences between glucose starved stationary and acid-induced stationary cells. Furthermore, they show that the physiology of stationary phase L. cremoris cells is multi-facetted and heterogeneous, and the presence of an energy source during stationary phase impacts the cells capacity to adapt to their environment.
pH-Dependent Mechanisms of Influenza Infection Mediated by Hemagglutinin
Authors: Caffrey Michael , Lavie Arnon
Published: December 2021

Influenza hemagglutinin (HA) is a viral membrane bound protein that plays a critical role in the viral life cycle by mediating entry into target cells. HA exploits the lowering of the pH in the endosomal compartment to initiate a series of conformational changes that promote access of the viral genetic material to the cytoplasm, and hence viral replication. In this review we will first discuss what is known about the structural properties of HA as a function of pH. Next, we will discuss the dynamics and intermediate states of HA. We will then discuss the specific residues that are thought to be titrated by the change in pH and possible mechanisms for the pH triggered conformational changes. Finally, we will discuss small molecules that disrupt the pH trigger and thus serve as potential therapeutic strategies to prevent influenza infection.
Physiopathological Relevance of D-Serine in the Mammalian Cochlea
Authors: Wang Jing , Serratrice Nicolas , Lee Cindy J. , François Florence , Sweedler Jonathan V. , Puel Jean-Luc , Mothet Jean-Pierre , Ruel Jérôme
Published: December 2021

NMDA receptors (NMDARs) populate the complex between inner hair cell (IHC) and spiral ganglion neurons (SGNs) in the developing and mature cochlea. However, in the mature cochlea, activation of NMDARs is thought to mainly occur under pathological conditions such as excitotoxicity. Ototoxic drugs such as aspirin enable cochlear arachidonic-acid-sensitive NMDAR responses, and induced chronic tinnitus was blocked by local application of NMDAR antagonists into the cochlear fluids. We largely ignore if other modulators are also engaged. In the brain, D-serine is the primary physiological co-agonist of synaptic NMDARs. Whether D-serine plays a role in the cochlea had remained unexplored. We now reveal the presence of D-serine and its metabolic enzymes prior to, and at hearing onset, in the sensory and non-neuronal cells of the cochlea of several vertebrate species. In vivo intracochlear perfusion of D-serine in guinea pigs reduces sound-evoked activity of auditory nerve fibers without affecting the receptor potentials, suggesting that D-serine acts specifically on the postsynaptic auditory neurons without altering the functional state of IHC or of the stria vascularis. Indeed, we demonstrate in vitro that agonist-induced activation of NMDARs produces robust calcium responses in rat SGN somata only in the presence of D-serine, but not of glycine. Surprisingly, genetic deletion in mice of serine racemase (SR), the enzyme that catalyzes D-serine, does not affect hearing function, but offers protection against noise-induced permanent hearing loss as measured 3 months after exposure. However, the mechanisms of activation of NMDA receptors in newborn rats may be different from those in adult guinea pigs. Taken together, these results demonstrate for the first time that the neuro-messenger D-serine has a pivotal role in the cochlea by promoting the activation of silent cochlear NMDAR in pathological situations. Thus, D-serine and its signaling pathway may represent a new druggable target for treating sensorineural hearing disorders (i.e., hearing loss, tinnitus).
Activity and Coupling to Hippocampal Oscillations of Median Raphe GABAergic Cells in Awake Mice
Authors: Jelitai Marta , Barth Albert M. , Komlósi Ferenc , Freund Tamás F. , Varga Viktor
Published: December 2021

Ascending serotonergic/glutamatergic projection from the median raphe region (MRR) to the hippocampal formation regulates both encoding and consolidation of memory and the oscillations associated with them. The firing of various types of MRR neurons exhibits rhythmic modulation coupled to hippocampal oscillatory activity. A possible intermediary between rhythm-generating forebrain regions and entrained ascending modulation may be the GABAergic circuit in the MRR, known to be targeted by a diverse array of top-down inputs. However, the activity of inhibitory MRR neurons in an awake animal is still largely unexplored. In this study, we utilized whole cell patch-clamp, single cell, and multichannel extracellular recordings of GABAergic and non-GABAergic MRR neurons in awake, head-fixed mice. First, we have demonstrated that glutamatergic and serotonergic neurons receive both transient, phasic, and sustained tonic inhibition. Then, we observed substantial heterogeneity of GABAergic firing patterns but a marked modulation of activity by brain states and fine timescale coupling of spiking to theta and ripple oscillations. We also uncovered a correlation between the preferred theta phase and the direction of activity change during ripples, suggesting the segregation of inhibitory neurons into functional groups. Finally, we could detect complementary alteration of non-GABAergic neurons’ ripple-coupled activity. Our findings support the assumption that the local inhibitory circuit in the MRR may synchronize ascending serotonergic/glutamatergic modulation with hippocampal activity on a subsecond timescale.
Comparing the MSIS-29 and the Health Utilities Index Mark III in Multiple Sclerosis
Authors: Marrie Ruth Ann , Dolovich Casandra , Cutter Gary R. , Fox Robert J. , Salter Amber
Published: December 2021

Objective: Since the properties of health-related quality of life measures vary across samples, studies directly comparing the properties of different measures can be useful in understanding their relative strengths and limitations. We aimed to compare the psychometric properties of the Health Utilities Index Mark III (HUI3) and the Multiple Sclerosis Impact Scale-29 (MSIS-29).

Methods: In Spring 2020, North American Research Committee on Multiple Sclerosis (NARCOMS) Registry participants completed the HUI3, MSIS-29, Patient Determined Disease Steps (PDDS) and SymptoMScreen. For the HUI3 and MSIS-29 we assessed floor and ceiling effects, construct validity, and internal consistency reliability. We used relative efficiency to compare the discriminating ability of the two measures with respect to disability.

Results: We included 5,664 participants in the analysis, with mean (SD) age 63 (10.1) years; 4,579 (80.8%) were women. For the HUI3 the mean (SD) score was 0.44 (0.32), for the MSIS-29 physical it was 34.0 (24.2) and for the MSIS-29 psychological it was 25.9 (20.4). Neither of the measures had floor or ceiling effects, and internal consistency reliability was > 0.70 for both. The HUI3 and MSIS-29 physical were strongly correlated (r = −0.78; 95%CI:−0.79,−0.77). The correlation between the HUI3 and MSIS-29 psychological was weaker but remained moderately strong (r = −0.64; 95%CI:−0.66,−0.63). After adjusting for sociodemographic and clinical factors, relative efficiency to discriminate between disability (PDDS) groups was highest for the MSIS-29 physical scale, followed by the HUI3.

Conclusion: Both measures had adequate validity and reliability. The MSIS-29 physical discriminated between disability groups better than the HUI3.
Optimal Transport Scenario With Rotary Air Transport for Access to Endovascular Therapy Considering Patient Outcomes and Cost: A Modeling Study
Authors: Wheaton Ashlee , Fok Patrick T. , Holodinsky Jessalyn K. , Vanberkel Peter , Volders David , Kamal Noreen
Published: December 2021

Background and Purpose: For an ischemic stroke patient whose onset occurs outside of the catchment area of a hospital that is capable of Endovascular Treatment (EVT) and whose stroke is suspected to be caused by a large vessel occlusion (LVO), a transportation dilemma exists. Bypassing the nearest stroke hospital will delay Alteplase but expedite EVT. Not bypassing allows for confirmation of an LVO diagnosis before transfer to an EVT-enabled facility, but ultimately delays EVT. Air transport can reduce a patient's overall time to treatment however, it is costly. We expanded on an existing model to predict where Drip-and-Ship vs. Mothership provides better outcomes by including rotary air transport, and we also included prediction of where either the transport method was most cost effective.

Methods: An existing model predicts the outcome of patients who screen positive for an LVO in the field based on how they were transported, Drip-and-Ship (alteplase-only facility first, then EVT-enabled facility) or Mothership (direct to EVT-enabled facility). In our model, the addition of rotary wing transportation was conditionally applied to inter-facility transfer scenarios where it provided a time advantage. Both patient outcome and transport cost functions were developed for Mothership and Drip-and-Ship strategies including transfers via either ground or air depending on the conditional probabilities. Experiments to model real world scenarios are presented by varying the driving time between the alteplase-only and EVT-enabled facility, time to treatment efficiencies at the alteplase-only facility, and EVT eligibility for LVO patients. Patient outcome and transport costs were evaluated for Mothership and Drip-and-Ship strategies.

Results: The results are presented in temporospatial diagrams that are color coded to indicate which strategy optimizes the objectives. In most regions, there was overall agreement between the optimal solution when considering patient outcomes or transport costs. Small regions exist where outcome and cost are divergent; however, the difference between the divergence in Mothership and Drip-and-Ship in these regions is marginal.

Conclusions: The optimal transport method can be optimized for both patient outcomes and transport costs.
Impact of Common Dizziness Associated Symptoms on Dizziness Handicap in Older Adults
Authors: Prell Tino , Wassermann Alexander , Zipprich Hannah M. , Finn Sigrid , Axer Hubertus
Published: December 2021

Background: A cross-sectional observational study was designed to determine the impact of dizziness associated symptoms on the dizziness handicap inventory (DHI) in older adults (≥60 years).

Methods: In total, 785 individuals referred to a multidisciplinary dizziness unit were assessed. Participants completed self-report questionnaires with general questions about symptoms of dizziness as well as the DHI. The DHI subscores (physical, functional, emotional) were calculated. Medical diagnoses were collected from the medical records of the patients. One-way MANOVA and networking analysis were used to analyze the impact of dizziness associated symptoms on dizziness handicap.

Results: Most patients reported swaying dizziness (60.6%) and feeling of unsteadiness (59.8%) with substantial overlap between the types of dizziness. Most frequent dizziness associated symptoms were ear noise/tinnitus, visual problems, and nausea/vomiting. Network analysis revealed that visual disturbances, headache, and hearing impairment were associated with higher DHI and explained 12% of the DHI variance in the linear regression. In the one-way MANOVA visual problems and headache had an effect on all three DHI subscores, while hearing impairment was associated with the functional and emotional subscores of DHI.

Conclusion: Distinct dizziness associated symptoms have substantial impact on dizziness handicap in older adults. A multifactorial assessment including these symptoms may assist in tailoring therapies to alleviate dizziness handicap in this group.
Gait Adaptation to a Phase-Specific Nociceptive Electrical Stimulation Applied at the Ankle: A Model to Study Musculoskeletal-Like Pain
Authors: Bertrand-Charette Michaël , Jeffrey-Gauthier Renaud , Roy Jean-Sébastien , Bouyer Laurent J.
Published: December 2021

Introduction: Lower limb pain, whether induced experimentally or as a result of a musculoskeletal injury, can impair motor control, leading to gait adaptations such as increased muscle stiffness or modified load distribution around joints. These adaptations may initially reduce pain but can also lead to longer-term maladaptive plasticity and to the development of chronic pain. In humans, many current experimental musculoskeletal-like pain models are invasive, and most don’t accurately reproduce the movement-related characteristics of musculoskeletal pain. The main objective of this study was to measure pain adaptation strategies during gait of a musculoskeletal-like experimental pain protocol induced by phase-specific, non-invasive electrical stimulation.

Methods: Sixteen healthy participants walked on a treadmill at 4 km/h for three consecutive periods (BASELINE, PAIN, and POST-PAIN). Painful electrical stimulations were delivered at heel strike for the duration of heel contact (HC) using electrodes placed around the right lateral malleolus to mimic ankle sprains. Gait adaptations were quantified bilaterally using instrumented pressure-sensitive insoles. One-way ANOVAs and group time course analyses were performed to characterize the impact of electrical stimulation on heel and forefoot contact pressure and contact duration.

Results: During the first few painful strides, peak HC pressure decreased on the painful side (8.6 ± 1.0%, p < 0.0001) and increased on the non-stimulated side (11.9 ± 0.9%, p < 0.0001) while HC duration was significantly reduced bilaterally (painful: 12.1 ± 0.9%, p < 0.0001; non-stimulated: 4.8 ± 0.8%, p < 0.0001). No clinically meaningful modifications were observed for the forefoot. One minute after the onset of painful stimulation, perceived pain levels stabilized and peak HC pressure remained significantly decreased on the painful side, while the other gait adaptations returned to pre-stimulation values.

Discussion: These results demonstrate that a non-invasive, phase-specific pain can produce a stable painful gait pattern. Therefore, this protocol will be useful to study musculoskeletal pain locomotor adaptation strategies under controlled conditions.
Neurotransmitters Affect Larval Development by Regulating the Activity of Prothoracicotropic Hormone-Releasing Neurons in Drosophila melanogaster
Authors: Hao Shun , Gestrich Julia Yvonne , Zhang Xin , Xu Mengbo , Wang Xinwei , Liu Li , Wei Hongying
Published: December 2021

Ecdysone, an essential insect steroid hormone, promotes larval metamorphosis by coordinating growth and maturation. In Drosophila melanogaster, prothoracicotropic hormone (PTTH)-releasing neurons are considered to be the primary promoting factor in ecdysone biosynthesis. Recently, studies have reported that the regulatory mechanisms of PTTH release in Drosophila larvae are controlled by different neuropeptides, including allatostatin A and corazonin. However, it remains unclear whether neurotransmitters provide input to PTTH neurons and control the metamorphosis in Drosophila larvae. Here, we report that the neurotransmitters acetylcholine (ACh) affect larval development by modulating the activity of PTTH neurons. By downregulating the expression of different subunits of nicotinic ACh receptors in PTTH neurons, pupal volume was significantly increased, whereas pupariation timing was relatively unchanged. We also identified that PTTH neurons were excited by ACh application ex vivo in a dose-dependent manner via ionotropic nicotinic ACh receptors. Moreover, in our Ca2+ imaging experiments, relatively low doses of OA caused increased Ca2+ levels in PTTH neurons, whereas higher doses led to decreased Ca2+ levels. We also demonstrated that a low dose of OA was conveyed through OA β-type receptors. Additionally, our electrophysiological experiments revealed that PTTH neurons produced spontaneous activity in vivo, which provides the possibility of the bidirectional regulation, coming from neurons upstream of PTTH cells in Drosophila larvae. In summary, our findings indicate that several different neurotransmitters are involved in the regulation of larval metamorphosis by altering the activity of PTTH neurons in Drosophila.
Merkel Cell Carcinoma: Evaluation of the Clinico-Pathological Characteristics, Treatment Strategies and Prognostic Factors in a Monocentric Retrospective Series (n=143)
Authors: Rastrelli Marco , Del Fiore Paolo , Russo Irene , Tartaglia Jacopo , Dal Monico Alessandro , Cappellesso Rocco , Nicolè Lorenzo , Piccin Luisa , Fabozzi Alessio , Biffoli Bernardo , Di Prata Claudia , Ferrazzi Beatrice , Dall’Olmo Luigi , Vecchiato Antonella , Spina Romina , Russano Francesco , Bezzon Elisabetta , Cingarlini Sara , Mazzarotto Renzo , Parisi Alessandro , Scarzello Giovanni , Pigozzo Jacopo , Brambullo Tito , Tropea Saveria , Vindigni Vincenzo , Bassetto Franco , Bertin Daniele , Gregianin Michele , Dei Tos Angelo Paolo , Cavallin Francesco , Alaibac Mauro , Chiarion-Sileni Vanna , Mocellin Simone
Published: December 2021

Background

Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin. The incidence of the disease has undergone a significant increase in recent years, which is caused by an increase in the average age of the population and in the use of immunosuppressive therapies. MCC is an aggressive pathology, which metastasizes early to the lymph nodes. These characteristics impose an accurate diagnostic analysis of the regional lymph node district with radiography, clinical examination and sentinel node biopsy. In recent years, there has been a breakthrough in the treatment of the advanced pathology thanks to the introduction of monoclonal antibodies acting on the PD-1/PD-L1 axis. This study aimed to describe the clinico-pathological characteristics, treatment strategies and prognostic factors of MCC.

Methods

A retrospective cohort study was conducted involving 143 consecutive patients who were diagnosed and/or treated for MCC. These patients were referred to the Veneto Institute of Oncology IOV-IRCCS and to the University Hospital of Padua (a third-level center) in the period between December 1991 and January 2020. In the majority of cases, diagnosis took place at the IOV. However, some patients were diagnosed elsewhere and subsequently referred to the IOV for a review of the diagnosis or to begin specific therapeutic regimens.

Results

143 patients, with an average age of 71 years, were affected mainly with autoimmune and neoplastic comorbidities. Our analysis has shown that age, autoimmune comorbidities and the use of therapy with immunomodulating drugs (which include corticosteroids, statins and beta-blockers) are associated with a negative prognosis. In this sense, male sex is also a negative prognostic factor.

Conclusions

Autoimmune and neoplastic comorbidities were frequent in the studied population. The use of drugs with immunomodulatory effects was also found to be a common feature of the population under examination. The use of this type of medication is considered a negative prognostic factor. The relevance of a multidisciplinary approach to the patient with MCC is confirmed, with the aim of assessing the risks and benefits related to the use of immunomodulating therapy in the individual patient.
Comparison of the Oncological Efficacy Between Intraoperative Radiotherapy With Whole-Breast Irradiation for Early Breast Cancer: A Meta-Analysis
Authors: He Lin , Zhou Jiejing , Qi Yuhong , He Dongjie , Yuan Canliang , Chang Hao , Wang Qiming , Li Gaiyan , Shao Qiuju
Published: December 2021

Background

Intraoperative radiotherapy (IORT) and whole-breast irradiation (WBI) are both effective radiotherapeutic interventions for early breast cancer patients undergoing breast-conserving surgery; however, an issue on whether which one can entail the better prognosis is still controversial. Our study aimed to investigate the 5-year oncological efficacy of the IORT cohort and the WBI cohort, respectively, and compare the oncological efficacy between the cohorts.

Materials and Methods

We conducted a computerized retrieval to identify English published articles between 2000 and 2021 in the PubMed, the Web of Science, the Cochrane Library, and APA PsycInfo databases. Screening, data extraction, and quality assessment were performed in duplicate.

Results

A total of 38 studies were eligible, with 30,225 analyzed participants. A non-comparative binary meta-analysis was performed to calculate the weighted average 5-year local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) in the two cohorts, respectively. The LRFS, DMFS, and OS (without restriction on the 5-year outcomes) between the two cohorts were further investigated by a comparative binary meta-analysis. The weighted average 5-year LRFS, DMFS, and OS in the IORT cohort were 96.3, 96.6, and 94.1%, respectively, and in the WBI cohort were 98.0, 94.9, and 94.9%, respectively. Our pooled results indicated that the LRFS in the IORT cohort was significantly lower than that in the WBI cohort (pooled odds ratio [OR] = 2.36; 95% confidential interval [CI], 1.66–3.36). Nevertheless, the comparisons of DMFS (pooled OR = 1.00; 95% CI, 0.76–1.31), and OS (pooled OR = 0.95; 95% CI, 0.79–1.14) between the IORT cohort with the WBI cohort were both not statistically significant.

Conclusions

Despite the drastically high 5-year oncological efficacy in both cohorts, the LRFS in the IORT cohort is significantly poorer than that in the WBI cohort, and DMFS and OS do not differ between cohorts.
Outcomes and Incidence of PF-ILD According to Different Definitions in a Real-World Setting
Authors: Torrisi Sebastiano Emanuele , Kahn Nicolas , Wälscher Julia , Polke Markus , Lee Joyce S. , Molyneaux Philip L. , Sambataro Francesca Maria , Heussel Claus Peter , Vancheri Carlo , Kreuter Michael
Published: December 2021

Background: Almost one-third of fibrosing ILD (fILDs) have a clinical disease behavior similar to IPF, demonstrating a progressive phenotype (PF-ILD). However, there are no globally accepted criteria on the definition of a progressive phenotype in non-IPF fILD yet. Four different definitions have been used; however, no internationally accepted definition currently exists.

Research Question: To compare the clinical and functional characteristics of progressive fILD according to the currently available definitions.

Study design and methods: Cases of fILD were identified retrospectively from the database of the tertiary referral center for ILD in Heidelberg. Lung function, clinical signs of progression, and radiological changes were evaluated. Patients with fILD were considered to have progression according to each of the four available definitions: Cottin (CO), RELIEF (RE), INBUILD (IN), and UILD study. Lung function changes, expressed as mean absolute decline of FVC%, were reported every 3 months following diagnosis and analyzed in the context of each definition. Survival was also analyzed.

Results: A total of 566 patients with non-IPF fILD were included in the analysis. Applying CO-, RE-, IN-, and UILD-definitions, 232 (41%), 183 (32%), 274 (48%), and 174 (31%) patients were defined as PF-ILD, respectively. RE- and UILD-criteria were the most stringent, with only 32 and 31% patients defined as progressive, while IN- was the most broad, with almost 50% of patients defined as progressive. CO- definition was in-between, classifying 41% as progressive. PF ILD patients with a UILD definition had worse prognosis.

Interpretation: Depending on the definition used, the existing criteria identify different groups of patients with progressive fILD, and this may have important prognostic and therapeutic implications.
QiShenYiQi Pills Attenuates Ischemia/Reperfusion-Induced Cardiac Microvascular Hyperpermeability Implicating Src/Caveolin-1 and RhoA/ROCK/MLC Signaling
Authors: Pan Chun-Shui , Yan Li , Lin Se-Qi , He Ke , Cui Yuan-Chen , Liu Yu-Ying , Hu Bai-He , Chang Xin , Zhao Xin-Rong , Fan Jing-Yu , Han Jing-Yan
Published: December 2021

Aims: Coronary microvascular hyperpermeability is an important contributor to ischemia or reperfusion (I/R) injury. However, the effective strategy for this insult remains limited. This study aimed to explore the protective effect of the compound Chinese medicine QiShenYiQi Pills (QSYQ) against coronary microvascular hyperpermeability after cardiac I/R with focusing on the underlying mechanism.

Methods and Results: Male Sprague-Dawley rats under anesthesia were subjected to occlusion of left coronary anterior descending artery followed by reperfusion. QSYQ was administrated 90 min before ischemia initiation. Human cardiac microvascular endothelial cells (HCMECs) underwent hypoxia or reoxygenation (H/R) challenge with QSYQ administrated 1 h prior to hypoxia. QSYQ exhibited effects on attenuating microvascular damage and albumin leakage after I/R injury, showing a role in maintaining endothelial junctions, caveolae, and collagen in basement membrane (BM) of microvessels. Study using HCMECs disclosed that QSYQ protected endothelial barrier from impairment by H/R, attenuating the decline of respiratory chain complex I and ATP synthase, activation of Src/caveolin-1 and increase of RhoA/ROCK/p-MLC, MMP-9, and CTSS. PP2, a Src inhibitor, partially imitated the effect of QSYQ.

Conclusions: The QSYQ was able to prevent I/R-induced cardiac microvascular hyperpermeability via a mechanism involving Src/caveolin-1 and RhoA/ROCK/MLC signaling.
Treatment With Lisinopril Prevents the Early Progression of Glomerular Injury in Obese Dahl Salt-Sensitive Rats Independent of Lowering Arterial Pressure
Authors: Brown Andrea K. , Nichols Alyssa , Coley Chantell A. , Ekperikpe Ubong S. , McPherson Kasi C. , Shields Corbin A. , Poudel Bibek , Cornelius Denise C. , Williams Jan M.
Published: December 2021

Recently, we reported that obese Dahl salt-sensitive leptin receptor mutant (SSLepRmutant) rats develop glomerular injury and progressive proteinuria prior to puberty. Moreover, this early progression of proteinuria was associated with elevations in GFR. Therefore, the current study examined whether treatment with lisinopril to reduce GFR slows the early progression of proteinuria in SSLepRmutant rats prior to puberty. Experiments were performed on 4-week-old SS and SSLepRmutant rats that were either treated with vehicle or lisinopril (20 mg/kg/day, drinking water) for 4 weeks. We did not observe any differences in MAP between SS and SSLepRmutant rats treated with vehicle (148 ± 5 vs. 163 ± 6 mmHg, respectively). Interestingly, chronic treatment with lisinopril markedly reduced MAP in SS rats (111 ± 3 mmHg) but had no effect on MAP in SSLepRmutant rats (155 ± 4 mmHg). Treatment with lisinopril significantly reduced proteinuria in SS and SSLepRmutant rats compared to their vehicle counterparts (19 ± 5 and 258 ± 34 vs. 71 ± 12 and 498 ± 66 mg/day, respectively). Additionally, nephrin excretion was significantly elevated in SSLepRmutant rats versus SS rats, and lisinopril reduced nephrin excretion in both strains. GFR was significantly elevated in SSLepRmutant rats compared to SS rats, and lisinopril treatment reduced GFR in SSLepRmutant rats by 30%. The kidneys from SSLepRmutant rats displayed glomerular injury with increased mesangial expansion and renal inflammation versus SS rats. Chronic treatment with lisinopril significantly decreased glomerular injury and renal inflammation in the SSLepRmutant rats. Overall, these data indicate that inhibiting renal hyperfiltration associated with obesity is beneficial in slowing the early development of glomerular injury and renal inflammation.
Effect of Kinesiology Tape on Muscle Activation of Lower Extremity and Ankle Kinesthesia in Individuals With Unilateral Chronic Ankle Instability
Authors: Yin Lulu , Liu Kun , Liu Chengmei , Feng Xiaodong , Wang Lin
Published: December 2021

Background: The purpose of the study was to determine the effect of kinesiology tape (KT) on lower limb muscle activation during computerized dynamic posturography (CDP) tasks and ankle kinesthesia in individuals with chronic ankle instability (CAI).

Methods: Thirty-five men with CAI participated in this study. The experimental procedure followed a repeated measures design. Muscle activation of lower extremity and ankle kinesthesia of participants were measured using four taping treatments, namely, KT, athletic tape (AT), sham tape (ST), and no tape (NT) in a randomized order. Muscle activation was assessed using surface electromyography (sEMG) synchronized with CDP tests from seven lower extremity muscles of the unstable limb. Ankle kinesthesia was measured by using a threshold to detect the passive motion direction of the unstable ankle. Parameters were analyzed by using a one-way repeated measures ANOVA and followed by pairwise comparisons with a Bonferroni correction.

Results: No significant difference was observed among different taping treatments for the majority of parameters during CDP. Except for condition 4 with open eyes, sway-referenced surface, and fixed surround in the sensory organization test (SOT), gastrocnemius medialis root mean square (RMS) was 28.19% lower in AT compared with NT (p = 0.021, 95% CI = 0.002–0.039), while gastrocnemius lateralis RMS was 20.25% lower in AT compared with KT (p = 0.038, 95% CI = 0.000–0.021). In forward-small sudden translation from motor control test (MCT), for peroneal longus (PL), RMS was 24.04% lower in KT compared with ST (p = 0.036, 95% CI = 0.000–0.018). In toes-down sudden rotation from adaption test (ADT), for PL, RMS was 23.41% lower in AT compared with ST (p = 0.015, 95% CI = 0.002–0.027). In addition, no significant difference was observed for a threshold to the detection of passive motion direction among different taping treatments.

Conclusion: This study indicated that KT had minimal effect on the muscle activation of the unstable lower limb during static stance, self-initiated, and externally triggered perturbation tasks from CDP and ankle kinesthesia among individuals with CAI, suggesting that the benefit of KT was too small to be clinically worthwhile during application for CAI.
Genome-Wide Association Study of Root Mealiness and Other Texture-Associated Traits in Cassava
Authors: Uchendu Kelechi , Njoku Damian Ndubuisi , Paterne Agre , Rabbi Ismail Yusuf , Dzidzienyo Daniel , Tongoona Pangirayi , Offei Samuel , Egesi Chiedozie
Published: December 2021

Cassava breeders have made significant progress in developing new genotypes with improved agronomic characteristics such as improved root yield and resistance against biotic and abiotic stresses. However, these new and improved cassava (Manihot esculenta Crantz) varieties in cultivation in Nigeria have undergone little or no improvement in their culinary qualities; hence, there is a paucity of genetic information regarding the texture of boiled cassava, particularly with respect to its mealiness, the principal sensory quality attribute of boiled cassava roots. The current study aimed at identifying genomic regions and polymorphisms associated with natural variation for root mealiness and other texture-related attributes of boiled cassava roots, which includes fibre, adhesiveness (ADH), taste, aroma, colour, and firmness. We performed a genome-wide association (GWAS) analysis using phenotypic data from a panel of 142 accessions obtained from the National Root Crops Research Institute (NRCRI), Umudike, Nigeria, and a set of 59,792 high-quality single nucleotide polymorphisms (SNPs) distributed across the cassava genome. Through genome-wide association mapping, we identified 80 SNPs that were significantly associated with root mealiness, fibre, adhesiveness, taste, aroma, colour and firmness on chromosomes 1, 4, 5, 6, 10, 13, 17 and 18. We also identified relevant candidate genes that are co-located with peak SNPs linked to these traits in M. esculenta. A survey of the cassava reference genome v6.1 positioned the SNPs on chromosome 13 in the vicinity of Manes.13G026900, a gene recognized as being responsible for cell adhesion and for the mealiness or crispness of vegetables and fruits, and also known to play an important role in cooked potato texture. This study provides the first insights into understanding the underlying genetic basis of boiled cassava root texture. After validation, the markers and candidate genes identified in this novel work could provide important genomic resources for use in marker-assisted selection (MAS) and genomic selection (GS) to accelerate genetic improvement of root mealiness and other culinary qualities in cassava breeding programmes in West Africa, especially in Nigeria, where the consumption of boiled and pounded cassava is low.
A Ratiometric Calcium Reporter CGf Reveals Calcium Dynamics Both in the Single Cell and Whole Plant Levels Under Heat Stress
Authors: Weigand Chrystle , Kim Su-Hwa , Brown Elizabeth , Medina Emily , Mares Moises , Miller Gad , Harper Jeffrey F. , Choi Won-Gyu
Published: December 2021

Land plants evolved to quickly sense and adapt to temperature changes, such as hot days and cold nights. Given that calcium (Ca2+) signaling networks are implicated in most abiotic stress responses, heat-triggered changes in cytosolic Ca2+ were investigated in Arabidopsis leaves and pollen. Plants were engineered with a reporter called CGf, a ratiometric, genetically encoded Ca2+ reporter with an mCherry reference domain fused to an intensiometric Ca2+ reporter GCaMP6f. Relative changes in [Ca2+]cyt were estimated based on CGf’s apparent KD around 220 nM. The ratiometric output provided an opportunity to compare Ca2+ dynamics between different tissues, cell types, or subcellular locations. In leaves, CGf detected heat-triggered cytosolic Ca2+ signals, comprised of three different signatures showing similarly rapid rates of Ca2+ influx followed by differing rates of efflux (50% durations ranging from 5 to 19 min). These heat-triggered Ca2+ signals were approximately 1.5-fold greater in magnitude than blue light-triggered signals in the same leaves. In contrast, growing pollen tubes showed two different heat-triggered responses. Exposure to heat caused tip-focused steady growth [Ca2+]cyt oscillations to shift to a pattern characteristic of a growth arrest (22%), or an almost undetectable [Ca2+]cyt (78%). Together, these contrasting examples of heat-triggered Ca2+ responses in leaves and pollen highlight the diversity of Ca2+ signals in plants, inviting speculations about their differing kinetic features and biological functions.
Regulation of Growth and Main Health-Promoting Compounds of Chinese Kale Baby-Leaf by UV-A and FR Light
Authors: He Rui , Li Yamin , Ou Shuying , Gao Meifang , Zhang Yiting , Song Shiwei , Liu Houcheng
Published: December 2021

Chinese kale baby leaves were hydroponically cultured under the basal light (Red: white LEDs = 2:3 at PPFD of 250 μmol·m−2·s−1) with different supplemental lighting, including individual ultraviolet-A (UV-A, 380 ± 10 nm, 20 μmol·m−2·s−1), far-red (FR, 735 ± 10 nm, 30 μmol·m−2·s−1) light, and their combination (UF) radiation in an artificial light plant factory. Effects of supplemental light qualities on morphology and physiology as well as health-promoting compounds of Chinese kale baby leaves were investigated. Application of UV-A and FR presented a positive effect on biomass, with a pronounced increase in petiole length, stem diameter, main stem length, and leaf area. Notably, plants under UF grew more vigorously than under other treatments. Higher levels of FRAP, vitamin C, total phenolic, and flavonoid were observed in plants under UV-A, while no striking changes or a decreasing trend recorded under FR and UF. Moreover, UV-A enhanced the glucosinolates (GLs) accumulation in Chinese kale baby leaves by increasing the predominant GLs (glucoraphanin and glucobrassicin) contents. RT-qPCR results indicated that UV-A upregulated the gene expressions of transcription factors and core structure genes related to GLs biosynthesis. However, downregulated or unchanged gene expressions of GLs biosynthesis-related genes in Chinese kale baby leaves were observed in FR and UF. Therefore, UV-A was benefited for the production of functional substances, while FR was conducive to a significant increase in crop yield. The combination of UV-A and FR, as a balance between yield and production of secondary metabolite, provided a new perspective for the application of artificial light in horticultural crop production.