bluuebunny/crossref_metadata_2025 huggingface dataset:
Presbyopia correction using the monocular bi-aspheric ablation profile in myopic eyes
Authors: Ryu Soyoung , Jun Ikhyun , Kang David S.Y. , Arba-Mosquera Samuel , Kim Harin , Jean Seung K. , Seo Kyoung Y. , Kim Eung K. , Kim Tae-im
Published: August 2022

Purpose:

To analyze the 6-month outcomes of the treatment combination of the monocular bi-aspheric ablation profile (PresbyMAX) and contralateral aspheric monofocal laser in situ keratomileusis (LASIK) ablation profile for correction of myopia and presbyopia.

Setting:

Yonsei University College of Medicine and Eyereum Eye Clinic, Seoul, South Korea.

Design:

Retrospective case series.

Methods:

This was a retrospective case review of 92 patients (184 eyes) diagnosed with myopia who underwent uneventful simultaneous bi-aspheric ablation in the nondominant eye and aspheric monofocal regular LASIK in the dominant eye to correct myopia and presbyopia between January 2017 and August 2020. Monocular and binocular uncorrected distance visual acuity (UDVA) and near visual acuity (UNVA), and corrected distance visual acuity and near visual acuity were analyzed postoperatively.

Results:

At 6 months postoperatively, the mean UDVAs (logMAR) in the dominant and nondominant eyes were 0.01 ± 0.02 and 0.26 ± 0.15, respectively. Furthermore, all treated dominant eyes achieved 20/20 or better monocular UDVA, and 84% achieved 20/16 or better monocular UDVA. In the nondominant treated eyes, 89% achieved 20/50 or better monocular UDVA, 78% achieved 20/40 or better, and 34% achieved 20/32 or better. The binocular cumulative UDVA at 6 months postoperatively was 20/20 or better in all patients. All patients achieved J2 or better in binocular cumulative UNVA, and 83% achieved J1.

Conclusions:

Presbyopia correction using the combination of PresbyMAX in the near eye and aspheric monofocal regular LASIK in the distant eye is a safe and effective treatment for presbyopia in patients with myopia.
Scleral-fixated and iris-fixated intraocular lens implantation or fixation:meta-analysis
Authors: Lau Tsz Hin Alexander , Garg Anubhav , Popovic Marko M. , Kertes Peter J. , Muni Rajeev H.
Published: August 2022

Scleral fixation and iris fixation are common intraocular lens (IOL) implantation techniques performed because of zonulopathy. There is a lack of consensus regarding their comparative efficacy and safety. This study aims to compare the efficacy and safety outcomes after scleral-fixated (SF) vs iris-fixated (IF) IOL implantation or fixation in adults. A systematic literature search was conducted on Ovid MEDLINE, Embase, and Cochrane CENTRAL from 2005 to 2020. 785 eyes from 2 randomized controlled trials and 9 nonrandomized studies were included. There was no significant difference in the mean corrected distance visual acuity at the final follow-up (P = .52) or absolute change in spherical equivalent (P = .88) between SF IOL and IF IOL implantation. The incidence of vitreous hemorrhage was significantly higher in the SF IOL group (risk ratio = 3.66, 95% CI, 1.16-11.55, P = .03). There were no differences in visual acuity and refractive outcomes between SF IOL and IF IOL implantation or fixation. Trade-offs in complications exist between the 2 techniques.
Insight of pancreatic cancer: recommendations for improving its therapeutic efficacy in the next decade
Authors: Xu Zhi-Hang , Wang Wen-Quan , Lou Wen-Hui , Liu Liang
Published: August 2022

Pancreatic cancer is one of the most malignant digestive system tumors. The effectiveness of pancreatic cancer treatment is still dismal, and the 5-year survival rate is only about 10%. Further improving the diagnosis and treatment of pancreatic cancer is the top priority of oncology research and clinical practice. Based on the existing clinical and scientific research experience, the review provides insight into the hotspots and future directions for pancreatic cancer, which focuses on early detection, early diagnosis, molecular typing and precise treatment, new drug development and regimen combination, immunotherapy, database development, model establishment, surgical technology and strategy change, as well as innovation of traditional Chinese medicine and breakthrough of treatment concept.
Pancreatic lymphangioma: two case reports from an institutional experience with a rare entity and review of literature
Authors: Tan-Garcia Alfonso , Lee Ser Yee , Wong Jen San , Ho Thomas W.T. , Ng Keng Sin , Tony Lim Kiat Hon
Published: August 2022

Pancreatic lymphangiomas are very rare benign cystic lesions that pose a diagnostic dilemma due to their resemblance to other non-neoplastic and neoplastic pancreatic cystic lesions. As such, pancreatic lymphangiomas are frequently diagnosed only after histological examination of the excised lesion. We present 2 cases of pancreatic lymphangioma, determine its prevalence at our institution and perform a detailed review of published literature since 2010. Case 1 is a 36-year-old male and case 2 is a 35-year-old female, both of which presented with abdominal pain. These were the only cases of pancreatic lymphangiomas reported at our institution since 2010. We reviewed 69 cases of pancreatic lymphangiomas from 52 publications. It affects predominantly females with a median age of 43 and such patients typically present with abdominal pain (58.8%) or are asymptomatic (27.9%). The median size is 8.6 cm, the most common location is the head of pancreas and the most common imaging finding is that of a multilocular cyst. Majority of patients underwent surgical resection (69.6%). Endoscopic ultrasound-guided fine-needle aspiration features of pancreatic lymphangiomas include chylous cyst fluid, elevated fluid triglyceride levels (15/16 cases) and numerous lymphocytes on cytology. The majority of patients with elevated fluid triglyceride levels (13/15 cases) were managed conservatively. Pancreatic lymphangiomas are rare pancreatic cystic lesions that may be diagnosed preoperatively using a multidisciplinary and multimodal approach involving clinical, radiological, biochemical and cytological features, allowing greater confidence in the selection of patients who can be managed conservatively.
The learning curve for robot-assisted distal pancreatectomy: a single-center experience of 301 cases
Authors: Xu Qiang , Liu Tiantong , Zou Xi , Li Pengyu , Gao Ruichen , Dai Menghua , Guo Junchao , Zhang Taiping , Liao Quan , Liu Ziwen , Wang Weibin , Cong Lin , Wu Wenming , Zhao Yupei
Published: August 2022

Objective:

Robotic distal pancreatectomy (RDP) has become a routine procedure in many pancreatic centers. This study aimed to describe a single-center experience with RDP since the first case, identify the learning curves of operation time and complication rate, and discuss the safety and feasibility of RDP.

Methods:

We collected and retrospectively analyzed the single-center surgical experience of 301 patients undergoing RDP at Peking Union Medical College Hospital (PUMCH) between 2012 and 2022 and described the change in operation proficiency and occurrence of perioperative complications in this observational study. The learning curve was assessed using the cumulative sum method.

Results:

We observed a three-phase pattern of RDP learning with operation time, complications, and postoperative pancreatic fistula as indicators and a two-phase pattern for spleening-preserving success. The mean operation time was 3.9 hours. The incidence rate of clinically significant postoperative pancreatic fistula (CRPOPF) was 17.9% and overall Clavien-Dindo complication rate (≥3) was 16.6%. The change of postoperative complicate rate was correlated with percentage of malignant cases.

Conclusion:

In the last decade, an evident decrease was seen in operation time, complication rate, and an increase in the spleen-preserving rate of distal pancreatectomy. With proper training, RDP is a safe and feasible procedure.
Machine Learning to Predict Hearing Preservation After Middle Cranial Fossa Approach for Sporadic Vestibular Schwannomas
Authors: Dixon Peter R. , Wojdyla Luke , Lee Joshua , Moshtaghi Omid , Claussen Alexander D. , Khan Usman A. , Mcdonald Marin A. , Schwartz Marc S. , Friedman Rick A.
Published: August 2022

Objective

Predict hearing preservation after middle cranial fossa approach for vestibular schwannomas.

Study Design

Application of machine learning algorithms, including classification and regression trees and random forest models to observational data.

Setting

Single-tertiary referral center.

Participants

Patients (n = 144) with a previously untreated sporadic vestibular schwannoma who underwent microsurgical resection by middle cranial fossa approach between November 2017 and November 2021.

Interventions

Middle cranial fossa approach.

Main Outcome and Measure(s)

Hearing preservation, defined by postoperative word recognition score of 50% or greater and pure tone average below 50 dB HL or less than 10% reduction in word recognition score. Model performance was evaluated with classification accuracy in an independent validation sample. Variable importance for the random forest model is reported according to entropy, a measure of mean decrease in model accuracy incurred by excluding each variable from the model.

Results

Hearing preservation was achieved in 60% of patients (86 of 144) overall. The classification and regression tree model identified preoperative pure tone average with a cut point of 30 dB HL, and more posterior tumor position to be the most important prognostic features for hearing preservation. Model accuracy was 0.68. The random forest model demonstrated perfect accuracy (1). Baseline pure tone average, word recognition score, and anteroposterior tumor position were among the most influential features for hearing preservation prediction.

Conclusion

Machine learning algorithms have the potential for accurate prediction of hearing preservation rates after middle fossa approach for vestibular schwannomas at a single institution. These models have the capacity for continued refinement with ongoing addition of data.
Hearing Loss Is Associated With Worse Socialization in the U.S. Hispanic Adult Population
Authors: Grewal Maeher R. , Golub Justin S.
Published: August 2022

Objective

The association between hearing loss and socialization has been characterized in limited detail and primarily among non-Hispanic Caucasians. We aimed to study this relationship using more detailed socialization measures than previously used and focusing on Hispanics.

Study Design

Cross-sectional epidemiologic study (Hispanic Community Health Study).

Setting

Multicentered, four U.S. communities.

Participants

U.S. Hispanics ages 18 to 76 years.

Main Measures

Multivariable linear regression controlling for confounders (age, sex, education) was conducted to analyze the association between hearing loss (four-frequency pure tone average) and socialization. Socialization was assessed with three independent surveys: a modified Cohen Interpersonal Support Evaluation List (ISEL), the Cohen Social Network Index (SNI), and a modified Moos Family Environment Scale.

Results

Average age was 46.7 years (standard deviation [SD], 13.6 yr; range, 18–75 yr). Average ISEL composite score was 25.9 (SD, 6.66; n = 4,330). Controlling for confounders, for every 10 dB worsening in hearing, the ISEL score decreased by 0.31 (95% confidence interval [CI], 0.08–0.52; p < 0.01). Average SNI network diversity score was 6.89 (SD, 1.81; n = 3,117) and average SNI network size was 15.4 individuals (SD, 8.11). Controlling for confounders, for every 10 dB worsening in hearing, the SNI network diversity decreased by 0.22 (95% CI, 0.15–0.29; p < 0.001), and SNI size decreased by 0.25 (95% CI, 0.07–0.62; p < 0.05). Average family cohesion score on the Moos Family Environment Scale was 12.9 (SD, 2.77; n = 4,234). Controlling for age, sex, and education, for every 10 dB worsening in hearing, family cohesion decreased by 0.14 (95% CI, 0.04–0.23; p < 0.01).

Conclusion

Hearing loss is associated with less social support, smaller/less diverse social networks, and less family cohesion in U.S. Hispanics.
Bacterial infection in coronavirus disease 2019 patients: co-infection, super-infection and how it impacts on antimicrobial use
Authors: Nedel Wagner , da Silveira Fernando , da Silva Cristofer Farias , Lisboa Thiago
Published: August 2022

Purpose of review

Since the beginning of the severe acute respiratory syndrome coronavirus 2 pandemic, there has been a large increase in the consumption of antimicrobials, both as a form of treatment for viral pneumonia, which has been shown to be ineffective, and in the treatment of secondary infections that arise over the course of the severe presentation of coronavirus disease 2019 (COVID-19). This increase in consumption, often empirical, ends up causing an increase in the incidence of colonization and secondary infections by multi and pan-resistant germs.

Recent findings

The presence of a hyperinflammatory condition induced by the primary infection, associated with the structural damage caused by viral pneumonia and by the greater colonization by bacteria, generally multiresistant, are important risk factors for the acquisition of secondary infections in COVID-19. Consequently, there is an increased prevalence of secondary infections, associated with a higher consumption of antimicrobials and a significant increase in the incidence of infections by multi and pan-resistant bacteria.

Antimicrobial stewardship and improvement in diagnostic techniques, improving the accuracy of bacterial infection diagnosis, may impact the antibiotic consumption and the incidence of infections by resistant pathogens.
Cosmetic Outcomes of Simple Pediatric Facial Lacerations Repaired With Skin Adhesive Compared With Skin Adhesive With Underlying Adhesive Strips
Authors: Munns Erin , Kienstra Andrew J. , Combs Patrick D. , Gabriele Giovanni , Wilkinson Matthew
Published: August 2022

Objectives

A randomized controlled trial was designed to compare 2 methods of repairing simple pediatric facial lacerations. We hypothesized that wounds repaired with skin adhesive and underlying adhesive strips compared with skin adhesive alone would be superior in regard to cosmetic outcome.

Methods

Patients aged younger than 18 years presenting to the emergency department with simple facial lacerations requiring repair were eligible for enrollment. Patients were randomly assigned to repair with either skin adhesive alone or skin adhesive with underlying adhesive strips. Families were contacted by phone 1 week after enrollment to discuss short-term complications. The cosmetic appearance of photographs of the scars at 2 months was analyzed using a visual analog scale by a blinded pediatric emergency physician and pediatric plastic surgeon.

Results

One hundred twenty patients were enrolled, with 92 returning for the 2-month follow-up. The visual analog scale scores for the skin adhesive with adhesive strips group were similar to the skin adhesive alone group (60 mm vs 58 mm, P = 0.540). Spearman ρ correlation coefficient between the raters was 0.669, indicating strong agreement. There was no significant difference in rates of return visits, wound dehiscence, or infection. The skin adhesive with adhesive strips group had a longer time to perform the repair (195 seconds vs 107 seconds, P < 0.001).

Conclusions

Using adhesive strips to first approximate a wound before applying skin adhesive leads to a similar cosmetic outcome compared with simple facial lacerations repaired with skin adhesive alone. Although the study showed longer time to complete the repair, this approach may still be useful in settings where approximation is difficult to obtain manually.
Biomechanical comparison of a 3D-printed prosthetic foot with conventional feet in people with transtibial amputation: A prospective cohort study
Authors: Trinler Ursula , Heitzmann Daniel W W , Hitzeroth Sebastian , Alimusaj Merkur , Rehg Mathias , Hogan Aidan
Published: August 2022

Introduction:

The method of 3D printing is increasingly gaining utilization in clinical applications and may support prosthetic fitting. The aim was to compare biomechanical outcomes of people with a transtibial amputation using a novel, individualizable, 3D-printed prosthetic foot (ComfyStep, Mecuris) with two conventional, widely used prosthetic feet during level ground walking using a 3D motion analysis system.

Methods:

Ten individuals with an unilateral transtibial amputation were fitted with 3 prosthetic feet (ComfyStep, Assure/Össur, DynamicMotion/Ottobock) using their current, well-fitting socket. They had at least 1 week of familiarization for each foot before gait analyses were conducted. Kinematics and kinetics as well as roll over shape (ROS) length and radius were calculated and compared between feet.

Results:

The sound side gait parameters of the participants were comparable when using different feet. However, there were differences on the affected side. The statistical analysis revealed that the 3D-printed foot differed significantly compared with the conventional feet in the following aspects: reduced range of motion, increased plantar flexion moment, reduced plantar flexion power, larger ROS radius, less favorable energy ratio, and higher overall stiffness.

Conclusion:

In principle, 3D-printed feet have advantages over conventional “off the shelf” feet, as their biomechanical characteristics could be adjusted more in detail according to the patient needs. Although, differences between conventional feet and the ComfyStep were shown. Whether these differences have a negative clinically relevant effect remains unclear. However, results suggest that commercially available 3D-printed feet should incorporate systematically better adjustments, for example, for stiffness, to enhance prosthetic performance.
Intense 68Ga-Pentixafor Activity in Idiopathic Retroperitoneal Fibrosis
Authors: Shu Qiaoqiao , Hu Mei , Deng Maoxue , Chen Yue , Cai Liang
Published: August 2022

A 52-year-old man was admitted to our hospital with lower abdominal and low back pain, and abdomen CT at an outside hospital presented a retroperitoneal mass with left urinary tract obstruction and hydronephrosis. In 68Ga-pentixafor PET/CT, the retroperitoneal mass showed intense radioactivity. Subsequently, the patient underwent biopsy of the retroperitoneal mass. The pathological examination showed only fibrous tissue without tumor cells. The patient was finally diagnosed with idiopathic retroperitoneal fibrosis. Our case demonstrated that idiopathic retroperitoneal fibrosis had intense uptake of 68Ga-pentixafor.
HOSPITAL CHARACTERISTICS ARE ASSOCIATED WITH CLINICAL OUTCOMES IN PATIENTS WITH CARDIOGENIC SHOCK
Authors: Bloom Jason E. , Nehme Ziad , Andrew Emily , Dawson Luke P. , Fernando Himawan , Noaman Samer , Stephenson Michael , Anderson David , Pellegrino Vincent , Cox Shelley , Lefkovits Jeffrey , Chan William , Kaye David M. , Smith Karen , Stub Dion
Published: August 2022

Background: Regionalized systems of care for the management of cardiogenic shock (CS) are increasingly being utilized. This study aims to assess whether receiving hospital characteristics such as the availability of 24-hour coronary angiography, on-site cardiac surgery, and annual treated CS volume influence outcomes in patients transferred by emergency medical services (EMS) to hospital with CS. Methods: This population-based cohort study included consecutive adult patients with CS who were transferred to hospital by EMS between January 1, 2015 and June 30, 2019 in Victoria, Australia. Data were obtained from individually linked ambulance, hospital, and state death index data sets. The primary outcome assessed was 30-day mortality stratified by the availability of 24-hour coronary angiography (cardiac center) at the receiving hospital. Results: A total of 3,217 patients were transferred to hospital with CS. The population had an average age of 67.9 +/− 16.1 years, and 1,289 (40.1%) were female. EMS transfer to a cardiac center was associated with significantly reduced rates of 30-day mortality (adjusted odds ratio [aOR], 0.78; 95% confidence interval [CI], 0.64–0.95), compared with noncardiac centers. Compared with the lowest annual CS volume quartile (<18 cases per year), hospitals in the highest volume quartile (>55 cases per year) had reduced risk of 30-day mortality (aOR, 0.71; 95% CI, 0.56–0.91). A stepwise reduction in the adjusted probability of 30-day mortality was observed in patients transferred by EMS to trauma level 1 centers (34.6%), compared with cardiothoracic surgical centers (39.0%), noncardiac surgical metropolitan (44.9%), and rural (51.3%) cardiac centers, all P < 0.05. Conclusion: Receiving hospital characteristics are associated with survival outcomes in patients with CS. These finding have important implications for establishing regionalized systems of care for patients with CS who are transferred to hospital by EMS.
EARLY INITIATION OF VASOPRESSIN REDUCES ORGAN FAILURE AND MORTALITY IN SEPTIC SHOCK
Authors: Rydz Alexandria C. , Elefritz Jessica L. , Conroy Megan , Disney Kathryn A. , Miller Christopher J. , Porter Kyle , Doepker Bruce A.
Published: August 2022

Purpose: The aim of the study is to determine whether initiating vasopressin earlier in septic shock reduces organ dysfunction and in-hospital all-cause mortality. Methods: This multicenter, retrospective, cohort study evaluated patients admitted to the medical intensive care unit between October 2011 and August 2018 with septic shock who received vasopressin within 48 hours of shock onset. The primary composite outcome was the proportion of patients with a change in the Sequential Organ Failure Assessment score greater than 3 from baseline to 72 hours after initiation of vasopressin and/or in-hospital all-cause mortality. Secondary outcomes included time to hemodynamic stability, acute kidney injury, and intensive care unit length of stay. Results: A total of 385 patients included in the final evaluation with a mean Acute Physiology and Chronic Health Evaluation II score of 31 and a mean baseline Sequential Organ Failure Assessment score of 13. Median time to initiation of vasopressin after norepinephrine was 7.3 hours. The primary composite outcome was significantly reduced in patients who had vasopressin initiated earlier in septic shock (odds ratio = 1.08, 95% confidence interval = 1.03–1.13, P < 0.001). After controlling for baseline data in a multivariable regression model the primary outcome remained statistically significant (odds ratio = 1.04, 95% confidence interval = 1.02–1.07, P = 0.001). Conclusions: Early initiation of vasopressin in septic shock may reduce the risk of in-hospital all-cause mortality and/or organ dysfunction.
A2A Adenosine Receptors Regulate Multiple Organ Failure After Hemorrhagic Shock in Mice
Authors: Kelestemur Taha , Nemeth Zoltan , Pacher Pal , Antonioli Luca , Haskó György
Published: August 2022

Trauma hemorrhagic shock (T/HS) is a clinical condition which causes multiple organ failure (MOF) that needs rapid intervention. Restricted oxygen at the cellular level causes inflammation and subsequent cell death. Adenosine triphosphate is the universal intracellular energy currency and an important extracellular inflammatory signaling molecule. Adenosine, an endogenous nucleotide formed as a result of the breakdown of adenosine triphosphate, is also released during T/HS. Adenosine binds to four G-protein-coupled receptors (A1, A2A, A2B, A3) called adenosine receptors or P1 receptors. In the present study, we evaluated the effect of activation, inactivation and genetic absence of A2aR (A2aR-/- mice) on T/HS-induced multiple organ failure. Wild-type mice were pretreated (30 minutes before shock induction) with an agonist or antagonist and then subjected to T/HS by withdrawing arterial blood and maintaining the blood pressure between 28 and 32 mmHg. A2aR-/- mice were subjected to T/HS in the absence of pharmacologic treatment. Neutrophil sequestration was assessed by detecting myeloperoxidase and Evans blue dye (EBD) method was used to analyze lung permeability. Blood and lung inflammatory cytokine levels were determined by sandwich ELISA. The liver enzymes aspartate transferase (AST) and alanine transaminase (ALT) were determined spectrophotometrically from plasma. Activation of the apoptotic cascade was evaluated using a mouse apoptosis array. Our results demonstrate that the selective A2aR agonist CGS21680 decreases lung neutrophil sequestration, lung pro-inflammatory cytokines IL-6 and TNF-α, and bronchoalveolar lavage EBD. Pretreatment with the selective antagonist ZM241385 and genetic blockade in A2aR-/- mice increased neutrophil sequestration, pro-inflammatory cytokine levels, and bronchoalveolar lavage fluid EBD. The myeloperoxidase level in the lung was also increased in A2aR-/- mice. We observed that anti-apoptotic markers decreased significantly with the absence of A2aR in the lung and spleen after T/HS. In conclusion, our data demonstrate that activation of A2aR regulates organ injury and apoptosis in the setting of T/HS.
Unmet Social Health Needs as a Driver of Inequitable Outcomes After Surgery
Authors: Taylor Kathryn K. , Neiman Pooja U. , Bonner Sidra , Ranganathan Kavitha , Tipirneni Renuka , Scott John W.
Published: August 2022

Objective:

This study aims to identify opportunities to improve surgical equity by evaluating unmet social health needs by race, ethnicity, and insurance type.

Background:

Although inequities in surgical care and outcomes based on race, ethnicity, and insurance have been well documented for decades, underlying drivers remain poorly understood.

Methods:

We used the 2008–2018 National Health Interview Survey to identify adults age 18 years and older who reported surgery in the past year. Outcomes included poor health status (self-reported), socioeconomic status (income, education, employment), and unmet social health needs (food, housing, transportation). We used logistic regression models to progressively adjust for the impact of patient demographics, socioeconomic status, and unmet social health needs on health status.

Results:

Among a weighted sample of 14,471,501 surgical patients, 30% reported at least 1 unmet social health need. Compared with non-Hispanic White patients, non-Hispanic Black, and Hispanic patients reported higher rates of unmet social health needs. Compared with private insurance, those with Medicaid or no insurance reported higher rates of unmet social health needs. In fully adjusted models, poor health status was independently associated with unmet social health needs: food insecurity [adjusted odds ratio (aOR)=2.14; 95% confidence interval (CI): 1.89–2.41], housing instability (aOR=1.69; 95% CI: 1.51–1.89), delayed care due to lack of transportation (aOR=2.58; 95% CI: 2.02–3.31).

Conclusions:

Unmet social health needs vary significantly by race, ethnicity, and insurance, and are independently associated with poor health among surgical populations. As providers and policymakers prioritize improving surgical equity, unmet social health needs are potential modifiable targets.
Capillimicrobium parvum gen. nov., sp. nov., a novel representative of Capillimicrobiaceae fam. nov. within the order Solirubrobacterales, isolated from a grassland soil
Authors: Vieira Selma , Huber Katharina J. , Geppert Alicia , Wolf Jacqueline , Neumann-Schaal Meina , Luckner Manja , Wanner Gerhard , Müsken Mathias , Overmann Jörg
Published: August 2022

The order

Solirubrobacterales

is a deep-branching lineage within the phylum

Actinomycetota

. Most representatives have been isolated from terrestrial environments. A strain isolated from a grassland soil was found to be affiliated with this order and therefore characterized by a polyphasic approach. Cells of strain 0166_1T are Gram-positive, short rods, non-motile, non-spore-forming and divide by binary fission. A surface layer with protrusions covers the majority of the cells. Strain 0166_1T grows optimally around neutral to slightly alkaline pH (pH 7.1–7.9) and at temperatures between 24–36 °C in SSE/HD 1 : 10 medium. It grows optimally with 0–0.5% NaCl (w/v) but can withstand concentrations up to 5 %. The major fatty acids are C18 : 1 ω9c, C16 : 1
 ω7c, C17 : 0 cyclo ω7c, C18 : 1
 ω7c methyl and C19 : 0 cyclo ω9c. The major polar lipids are diphosphatidylglycerol, two unidentified phospholipids and one unidentified glycolipid. MK-7(H4) and MK-7(H2) are the predominant respiratory quinones. meso-2,6-Diaminopimelic acid is the diagnostic diamino acid in the cell-wall peptidoglycan. The G+C content for strain 0166_1T is 72.8 mol%. 16S rRNA gene sequence analysis indicated that this bacterium was related to

Conexibacter arvalis

KV-962T and

Conexibacter stalactiti

YC2-25T with 95.5 and 95.2 % sequence similarity, respectively. Based on the phenotypic, genomic and phylogenetic data, we propose the novel species Capillimicrobium parvum sp. nov. (type strain 0166_1T=DSM 104329T=LMG 29999T=CECT 9240T) of the novel genus Capillimicrobium gen. nov. within the novel family Capillimicrobiaceae fam. nov.
Screening Immunotherapy Targets to Counter Radiation-Induced Neuroinflammation
Authors: Sharma Sadhana , Fallgreen Christina , Weil Michael M. , Chatterjee Anushree , Nagpal Prashant
Published: August 2022

Galactic cosmic rays (GCR) in space induce increase in cerebral amyloid-β levels and elevated levels of microgliosis and astrocytosis, causing accelerated neurodegeneration from this increased neuroinflammation. Even exposure to low-levels of high-Z high-energy (HZE) radiation (50 cGy) has been shown to induce biochemical and immunohistochemical changes in short-term leading to degradation in cognition, motor skills, and development of space-induced neuropathy. There is lack of effective neuroinflammation countermeasures, and current experimental therapies require invasive intracerebral and intrathecal delivery due to difficulty associated with therapeutic crossover between blood-brain barrier. Here, we present a new countermeasure development approach for neurotherapeutics using high-throughput drug-discovery, target validation, and lead molecule identification with nucleic acid-based molecules. These Nanoligomer™ molecules are rationally designed using a bioinformatics and AI-based ranking method and synthesized as a single-modality combining 6-different design elements to up- or down-regulate gene expression of target gene at will, resulting in elevated or diminished protein expression of intended target. This platform approach was used to perturb and identify most effective upstream regulators and canonical pathways for therapeutic intervention to reverse radiation-induced neuroinflammation. The lead Nanoligomer™ and corresponding target granulocyte-macrophage colony-stimulating factor (GM-CSF) were identified usingin vitrocell-based screening in human astrocytes and donor derived peripheral blood mononuclear cells (PBMCs) and further validatedin vivousing a mouse model of radiation-induced neuroinflammation. GM-CSF transcriptional downregulator Nanoligomer 30D.443_CSF2 downregulated proinflammatory cytokine GM-CSF (or CSF2) using simple intraperitoneal injection of low-dose (3mg/kg) and completely reversed expression of CSF2 in cortex tissue, as well as other neuroinflammation markers. These results point to the broader applicability of this approach towards space countermeasure development, and potential for further investigation of lead neurotherapeutic molecule as a reversible gene therapy.
spARC recovers human glioma spatial signaling networks with graph filtering
Authors: Kuchroo Manik , Miyagishima Danielle F. , Steach Holly R. , Godavarthi Abhinav , Takeo Yutaka , Duy Phan Q. , Barak Tanyeri , Erson-Omay E. Zeynep , Youlten Scott , Mishra-Gorur Ketu , Moliterno Jennifer , McGuone Declan , Günel Murat , Krishnaswamy Smita
Published: August 2022

Biological networks operate within architectural frameworks that influence the state and function of cells through niche-specific factors such as exposure to nutrients and metabolites, soluble signaling molecules, and direct cognate cell-cell communication. Spatial omics technologies incorporate environmental information into the study of biological systems, where the spatial coordinates of cells may directly or indirectly encode these micro-anatomical features. However, they suffer from technical artifacts, such as dropout, that impede biological discovery. Current methods that attempt to correct for this fail to adequately integrate highly informative spatial information when recovering gene expression and modelling cell-cell dynamicsin situ. To address this oversight, we developed spatial Affinity-graph Recovery of Counts (spARC), a data diffusion-based filtration method that shares information between neighboring cells in tissue and related cells in expression space, to recover gene dynamics and simulate signalling interactions in spatial transcriptomics data. Following validation, we applied spARC to 10 IDH-mutant surgically resected human gliomas across WHO grades II-IV in order to study signaling networks across disease progression. This analysis revealed co-expressed genes that border the interface between tumor and tumor-infiltrated brain, allowing us to characterize global and local structure of glioma. By simulating paracrine signalingin silico, we identified an Osteopontin-CD44 interaction enriched in grade IV relative to grade II and grade III astrocytomas, and validated the clinical relevance of this signaling axis using TCGA.
Atypical speech production of multisyllabic words and phrases by children with developmental dyslexia
Authors: Keshavarzi Mahmoud , Liberto Giovanni M. Di , Gabrielczyk Fiona , Wilson Angela , Macfarlane Annabel , Goswami Usha
Published: August 2022

The prevalent ‘core phonological deficit’ model of dyslexia proposes that the reading and spelling difficulties characterizing affected children stem from prior developmental difficulties in processing speech sound structure, for example perceiving and identifying syllable stress patterns, syllables, rhymes and phonemes. Yet spoken word production appears normal. This suggests an unexpected disconnect between speech input and speech output processes. Here we investigated the output side of this disconnect from a speech rhythm perspective by measuring the speech amplitude envelope (AE) of multisyllabic spoken phrases. The speech AE contains crucial information regarding stress patterns, speech rate, tonal contrasts and intonational information. We created a novel computerized speech copying task in which participants copied aloud familiar spoken targets like “Aladdin”. Seventy-five children with and without dyslexia were tested, some of whom were also receiving an oral intervention designed to enhance multi-syllabic processing. Similarity of the child’s productions to the target AE was computed using correlation and mutual information metrics. Similarity of pitch contour, another acoustic cue to speech rhythm, was used for control analyses. Children with dyslexia were significantly worse at producing the multi-syllabic targets as indexed by both similarity metrics for computing the AE. However, children with dyslexia were not different from control children in producing pitch contours. Accordingly, the spoken production of multisyllabic phrases by children with dyslexia is atypical regarding the AE. Children with dyslexia may not appear to listeners to exhibit speech production difficulties because their pitch contours are intact.

Research Highlights

Speech production of syllable stress patterns is atypical in children with dyslexia.

Children with dyslexia are significantly worse at producing the amplitude envelope of multi-syllabic targets compared to both age-matched and reading-level-matched control children.

No group differences were found for pitch contour production between children with dyslexia and age-matched control children.

It may be difficult to detect speech output problems in dyslexia as pitch contours are relatively accurate.
Interpretable Chirality-Aware Graph Neural Network for Quantitative Structure Activity Relationship Modeling in Drug Discovery
Authors: Liu Yunchao “Lance” , Wang Yu , Vu Oanh , Moretti Rocco , Bodenheimer Bobby , Meiler Jens , Derr Tyler
Published: August 2022

In computer-aided drug discovery, quantitative structure activity relation models are trained to predict biological activity from chemical structure. Despite the recent success of applying graph neural network to this task, important chemical information such as molecular chirality is ignored. To fill this crucial gap, we proposeMolecular-KernelGraphNeuralNetwork (MolKGNN) for molecular representation learning, which features SE(3)-/conformation invariance, chiralityawareness, and interpretability. For our MolKGNN, we first design a molecular graph convolution to capture the chemical pattern by comparing the atom’s similarity with the learnable molecular kernels. Furthermore, we propagate the similarity score to capture the higher-order chemical pattern. To assess the method, we conduct a comprehensive evaluation with nine well-curated datasets spanning numerous important drug targets that feature realistic high class imbalance and it demonstrates the superiority of MolKGNN over other GNNs in CADD. Meanwhile, the learned kernels identify patterns that agree with domain knowledge, confirming the pragmatic interpretability of this approach. Our codes are publicly available athttps://github.com/meilerlab/MolKGNN.
Stac1 Regulates Sensory Stimulus Induced Escape Locomotion
Authors: Linsley Jeremy W. , Perez Nadia , Hsu I-Uen , Yang Yuyang , Jasti Naveen , Waalkes Matthew , Horstick Eric J. , Kuwada John Y.
Published: August 2022

The stac family of genes are expressed by several cell types including neurons and muscles in a wide variety of animals. In vertebrates, stac3 encodes an adaptor protein specifically expressed by skeletal muscle that regulates L-type calcium channels (CaChs) and excitation-contraction coupling. The function of Stac proteins expressed by neurons in the vertebrate CNS, however, is unclear. To better understand neuronal Stac proteins, we identified the stac1 gene in zebrafish. stac1 is expressed selectively in the embryonic CNS including in Kolmer-Agduhr (KA) neurons, the cerebral fluid-contacting neurons (CSF-cNs) in the spinal cord. Previously CSF-cNs in the spinal cord were implicated in locomotion by zebrafish larvae. Thus, expression of stac1 by CSF-cNs and the regulation of CaChs by Stac3 suggest the hypothesis that Stac1 may be important for normal locomotion by zebrafish embryos. We tested to see if optogenetic activation of CSF-cNs was sufficient to induced swimming in embryos as it is in larvae. Indeed, optogenetic activation of CSF-cNs in embryos induced swimming in embryos. Next, we generated stac1-/- null embryos and found that both mechanosensory and noxious stimulus-induced swimming were decreased. We further found that zebrafish embryos respond more vigorously to tactile stimulation in the light compared to the dark. Interestingly, light enhancement of touch-induced swimming was eliminated in stac1 mutants. Thus, Stac1 regulates escape locomotion in zebrafish embryos perhaps by regulating the activity of CSF-cNs.

SIGNIFICANCE STATEMENT

The stac genes are a small family of genes found in neurons and muscle in both vertebrates and invertebrates. Stac3 is a muscle protein that controls excitation-contraction coupling via regulation of L-type calcium channels and in humans a STAC3 mutation is responsible for a congenital myopathy. The function of neural Stac proteins, however, is unknown in vertebrates. The findings of this report show that neural stac1 is expressed by cerebral fluid-contacting neurons (CSF-cNs) in the spinal cord of zebrafish embryos and that it is necessary for normal sensory stimulus induced escape swimming. To our knowledge this is the first demonstration of a function for stac genes in neurons in the vertebrate nervous system.
Fan cells in lateral entorhinal cortex directly influence medial entorhinal cortex through synaptic connections in layer 1
Authors: Vandrey Brianna , Armstrong Jack , Brown Christina M. , Garden Derek L. F. , Nolan Matthew F.
Published: August 2022

Standard models for spatial and episodic memory suggest that the lateral entorhinal cortex (LEC) and medial entorhinal cortex (MEC) send parallel independent inputs to the hippocampus, each carrying different types of information. Here, we evaluate the possibility that information is integrated between divisions of the entorhinal cortex prior to reaching the hippocampus. We demonstrate that fan cells in layer 2 (L2) of LEC that receive neocortical inputs, and that project to the hippocampal dentate gyrus, also send axon collaterals to layer 1 (L1) of the MEC. Activation of fan cell inputs evokes monosynaptic glutamatergic excitation of stellate and pyramidal cells in L2 of the MEC, typically followed by inhibition that contains fast and slow components mediated by GABAA and GABAB receptors, respectively. Fan cell inputs also directly activate interneurons in L1 and L2 of MEC, with synaptic connections from L1 interneurons accounting for slow feedforward inhibition of L2 principal cell populations. The relative strength of excitation and inhibition following fan cell activation differs substantially between neurons and is largely independent of anatomical location. Our results demonstrate that the LEC, in addition to directly influencing the hippocampus, can activate or inhibit major hippocampal inputs arising from the MEC. Thus, local circuits in the superficial MEC may combine spatial information with sensory and higher order signals from the LEC, providing a substrate for integration of ‘what’ and ‘where’ components of episodic memories.
The Origin of Cysteine and its Catabolism in Mammalian Tissues and Tumors
Authors: Yoon Sang Jun , Combs Joseph A. , Falzone Aimee , Prieto-Farigua Nicolas , Caldwell Samantha , Ackerman Hayley D. , Flores Elsa R. , DeNicola Gina M.
Published: August 2022

Cysteine plays critical roles in cellular biosynthesis, enzyme catalysis, and is an essential contributor to redox metabolism. While cultured cells are highly dependent on exogenous cystine for proliferation and survival, how diverse tissues obtain and use cysteine in vivo has not been characterized. We comprehensively interrogated cysteine metabolism in normal murine tissues and the cancer that arise from them using stable isotope 13C-serine and 13C-cystine tracing. We found that de novo cysteine synthesis was highest in normal liver and pancreas and absent in lung tissue. In tumors, cysteine synthesis was either inactive or downregulated during tumorigenesis. By contrast, cystine uptake and metabolism to downstream metabolites was a universal feature of normal tissues and tumors. Differences in cysteine catabolism were evident across tumor types, including glutathione synthesis. Thus, cystine is a major contributor to the cysteine pool in tumors and cysteine catabolic pathways are differentially active across tumor types.
Subclinical Atherosclerosis is Associated with Discrepancies in BAFF and APRIL Levels and Altered Breg Potential of Precursor-like Marginal Zone B-Cells in HIV Treated Individuals
Authors: Aranguren Matheus , Doyon-Laliberté Kim , El-Far Mohamed , Chartrand-Lefebvre Carl , Routy Jean-Pierre , Barril Jean Guy , Trottier Benoît , Tremblay Cécile , Durand Madeleine , Poudrier Johanne , Roger Michel ,   Canadian HIV and Aging Cohort Study
Published: August 2022

Chronic inflammation persists in people living with HIV (PLHIV) despite antiretrovial therapy (ART), and is involved in their premature development of cardiovascular diseases (CVD) such as atherosclerosis. We have previously reported that an excess of “B-cell activating factor” (BAFF), an important molecule for the selection and activation of first line Marginal Zone (MZ) B-cell populations, is associated with deregulations of precursor-like MZ (MZp), whose potent B-cell regulatory (Breg) capacities are altered in PLHIV, early on and despite 1-2 years of ART. Based on these observations, and growing evidence that MZ populations are involved in atherosclerosis control, we designed a cross sectional study to explore the associations between BAFF and its analogue “A proliferation-inducing ligand” (APRIL) with subclinical CVD in long time treated individuals of the Canadian HIV and Aging Cohort Study (CHACS) imaging sub-study group. We also characterized the Breg profile of MZp from the blood of these individuals. Results were correlated with the total volume of atherosclerotic plaques (TPV) and with CVD risk factors and biomarkers. TPV was measured using cardiac computerised tomography angiography, and presence of CVD was defined as TPV > 0. We report that blood levels of BAFF are elevated and correlate positively with CVD and its risk factors in PLHIV from the CHACS, in contrast to APRIL levels, which correlate negatively with these factors. Expression levels of Breg markers such as NR4A3, CD39, CD73 and CD83 are significantly lower in PLHIV when compared to those of HIV-uninfected controls. In vitro experiments show that APRIL upregulates the expression of Breg markers by blood MZp from HIV-uninfected individuals, while this modulation is dampened by the addition of recombinant BAFF. Altogether, our observations suggest that strategies viewed to modulate levels of BAFF and/or APRIL could eventually represent a potential treatment target for CVD in PLHIV.
Crystal structure and Hirshfeld surface analysis of ethyl 2′-amino-5-bromo-3′-cyano-6′-methyl-2-oxospiro[indoline-3,4′-pyran]-5′-carboxylate
Authors: Naghiyev Farid N. , Khrustalev Victor N. , Venskovsky Nikolai U. , Akkurt Mehmet , Khalilov Ali N. , Bhattarai Ajaya , Mamedov İbrahim G.
Published: August 2022

The crystal used for structure determination contained, along with the title compound, C17H14BrN3O4, an admixture [0.0324 (11)] of its 7-bromo isomer. The 2,3-dihydro-1H-indole ring system is nearly planar, while the conformation of the 4H-pyran ring is close to a flattened boat. The mean planes of these fragments form a dihedral angle of 86.67 (9)°. The carboxylate group lies near the plane of 4H-pyran, its orientation is stabilized by an intramolecular C—H...O contact. In the crystal, the molecules are connected into layers by N—H...N and N—H...O hydrogen bonds. The most important contributions to the crystal packing are from H...H (33.1%), O...H/H...O (16.3%), N...H/H...N (12.1%), Br...H/H...Br (11.5%) and C...H/H...C (10.6%) interactions.
Syntheses and crystal structures of 4-(4-methoxyphenyl)piperazin-1-ium 4-methylbenzoate monohydrate and bis[4-(4-methoxyphenyl)piperazin-1-ium] benzene-1,2-dicarboxylate
Authors: Shankara Prasad Holehundi J. , Devaraju  , Vinaya  , Yathirajan Hemmige S. , Parkin Sean R. , Glidewell Christopher
Published: August 2022

Co-crystallization of N-(4-methoxyphenyl)piperazine with 4-methylbenzoic acid and with benzene-1,2-dicarboxylic acid yields the salts 4-(4-methoxyphenyl)piperazin-1-ium 4-methylbenzoate monohydrate, C11H17N2O+·C8H7O2
−·H2O (I), and bis[4-(4-methoxyphenyl)piperazin-1-ium] benzene-1,2-dicarboxylate, 2C11H17N2O+·C8H4O4
2− (II). These salts both crystallize with Z′ = 2, in space groups P\overline{1} and Pna21, respectively. In compound (I), a combination of four O—H...O, four N—H...O, one C—H...O and one C—H...π(arene) hydrogen bonds link the six independent components into complex sheets, within which the two piperazine rings, the two anions, and the two water molecules are related by an approximate, non-crystallographic translation along the b-axis direction. In compound (II), sheets containing R
4
4(18) and R
10
12(38) rings are formed by the combined action of eight independent N—H...O hydrogen bonds. Comparisons are made with the structures of some related compounds.