bluuebunny/crossref_metadata_2025 huggingface dataset:
Landscape of genetic counseling in the Philippines
Authors: Abad Peter James , Tumulak Ma‐Am Joy , Guerbo Romer , de Castro‐Hamoy Leniza , Bautista Niecy Grace , Nuique Ramonito , Jacalan Frances Isabelle , Talapian Gay Luz , Felipe‐Dimog Eva Belingon , Lagarde John Benedict , Plaga Starlene Joy , Jover Edbert Jasper , Morales Kristine Dawn , Canoy Graciel Mae , Laurino Mercy Y.
Published: October 2023

In this paper, we report on the professional development of genetic counselors in the Philippines as we discuss the status of genetic counseling training and research, along with the roles and scope of practice of genetic counselors. The development of a master's level training program for non‐physician genetic counselors in the Philippines initiated in 2011 was in response to the increasing demand for genetic counseling services. There are currently 18 locally trained genetic counselors who are practicing in various fields including newborn screening, pediatrics, cancer, prenatal and preconception, neurology, and research. Despite the success of the genetic counseling training program, various professional challenges hinder maximizing the impact of genetic counselors in the health system. The challenges discussed in this paper include the limited number of genetic counselors, the lack of government positions officially recognizing the ‘genetic counselor’ title, and the absence of a regulatory framework. These issues require thorough discussion with appropriate government agencies and collaboration with other healthcare professional organizations with the ultimate goal of ensuring quality genetic counseling services nationwide.
Reproductive justice advocacy efforts among genetic counselors and family planning providers
Authors: Johnstonbaugh Hannah Z. , Lee Jessica K. , Semesky Patrick , Sagaser Katelynn G.
Published: October 2023

Throughout all areas of medical practice, genetic counselors (GCs) occupy a key position in promoting patients' personal autonomy while facilitating informed medical decision‐making. This professional position aligns with the concept of reproductive justice. Previous literature has attempted to define reproductive advocacy in medicine as well as the potential intersection of genetic counseling and reproductive justice advocacy work, yet limited data exist regarding GCs' perceptions of their role and involvement in reproductive justice advocacy work. This study aimed to identify the perceptions and actions of GCs regarding reproductive justice advocacy measures, as well as explore motivating factors influencing their attitudes and behaviors. Family planning providers, who tend to prioritize reproductive justice and advocacy, were surveyed to be a comparison group. We distributed an anonymous online survey within the National Society of Genetic Counselors (NSGC) and the Society of Family Planning (SFP) consisting of a 10‐item personality inventory and Likert scale questions exploring characteristics and behaviors regarding reproductive justice advocacy. Results from 252 eligible respondents were analyzed using descriptive statistics, Chi‐square, and Mann–Whitney U analyses. NSGC members are significantly less involved in several areas of reproductive justice advocacy, including regular participation in advocacy efforts when compared to SFP members (p = 0.04). The most cited barrier to NSGC members' participation was feeling unsure how to become involved, a significant difference compared to SFP members (p = 0.01). Findings from this study, undertaken in the final days of Roe v. Wade, suggest that GCs want to be more involved in reproductive justice advocacy but are uncertain where to begin. Intersociety collaboration and intra‐society promotion of grassroots reproductive justice efforts may reduce this perceived barrier and others like it.
The potential impact of implementation of expanded carrier screening on pediatric patient diagnoses: A retrospective chart review of patients who receive care in an outpatient genetics clinic in the northeast
Authors: Roche Kelly , Khan Shama P. , Botti Christina , Giampietro Philip , Anderson Sharon , Ashkinadze Elena
Published: October 2023

The use of expanded carrier screening (ECS) to assess reproductive risk for autosomal recessive (AR) or X‐linked recessive (XLR) conditions has been increasingly integrated into obstetrical care. The aim of this study was to determine what proportion of pediatric patients seen by a medical genetics practice could have had their diagnosis predicted if the parent(s) had undergone currently available ECS at the time of data collection in 2021. A retrospective chart review of patients seen for a medical genetic evaluation at a large academic institution was performed from June 1, 2017, through June 1, 2020. At this institution, 8% of patients were diagnosed with an AR or XLR condition. Of these patients, 61% of the diagnoses could have been predicted in advance if the parent(s) had undergone ECS via the panel referenced in this study. The results of this study highlight the broad range of conditions currently seen in a clinical setting that could be identified as a risk prior to or during pregnancy via ECS. In the prenatal setting, ascertainment of reproductive risk via ECS enables prospective parents to undertake interventions such as prenatal and preimplantation genetic diagnosis. For parents who decline reproductive risk‐reducing measures, knowledge about neonatal risk allows for prompt confirmatory testing. In the pediatric setting, the option of early and focused testing can benefit affected individuals and their families.
Implementation of a dedicated cascade testing clinic for patients at risk for hereditary cancer syndromes
Authors: Jacobs Michelle F. , Koeppe Erika S. , Chase Colby L. , Martinez Julia , Henry Marie‐Louise , Osborne Jenae M. , Stoffel Elena M. , Quinonez Shane C.
Published: October 2023

Cascade testing, the site‐specific genetic testing of relatives within families with an inherited condition, is underutilized. Long wait times for appointments in specialty genetics clinics are a known barrier to genetic testing access. In our cancer genetics, New Patient Clinic (NPC), the long wait time for an appointment (on average 5 months for routine referrals), was identified by both providers and patients as a barrier to uptake of cascade testing. Timely testing of at‐risk relatives is essential to maximize the benefits of cascade testing and reduce cancer morbidity and mortality. Our objective was to improve access via implementation of a different clinical model that designated appointments for patients seeking cascade testing. A secondary goal was to improve use of genetic counselor time. We implemented a dedicated Cascade Testing Clinic (CTC) with an expedited triaging and unique scheduling model to decrease patient wait time to appointment and optimize clinician time. We report on the process and outcomes here. Between October 2016 and February 2020, the average wait time between referral date and first scheduled appointment date was 46 days for the CTC compared to 144 days for the NPC (p < 0.0001). No‐show/cancelation/rescheduling rate was 11.7% in the CTC compared to 29.7% in the NPC (p < 0.0001). Genetic counselors saw approximately twice as many patients per half‐day clinic in the CTC compared to the NPC (p < 0.00001). Modifications to clinic staffing and appointment times were made based on provider feedback. Implementation of a dedicated clinic specifically for patients seeking cascade testing significantly shortened wait times for this population, reduced patient drop‐off, and improved clinician efficiency. The relatively straightforward indications and generally uncomplicated medical histories made this an ideal population for expedited appointments.
Higher HBeAg‐reversion virological relapse and lower sustained remission after treatment cessation in tenofovir‐treated HBeAg‐positive patients
Authors: Chen Yi‐Cheng , Hsu Chao‐Wei , Chien Rong‐Nan
Published: October 2023

A complete investigation of the clinical outcomes after treatment cessation in HBeAg‐positive patients with HBeAg loss is limited. We retrospectively recruited 242 HBeAg‐positive patients with HBeAg loss after a median duration of 37.2 months with tenofovir (TDF, n = 77) or entecavir (ETV, n = 165) treatment. There were 77 (31.8%) patients with sustained virological remission (SVR), 85 (35.1%) with HBeAg‐reversion virological relapse, 80 (33.1%) with HBeAg‐negative virological relapse after treatment cessation, and 23 (9.5%) with HBsAg loss. Clinical data at baseline, on‐treatment and during off‐treatment follow‐up were analyzed. The 3‐year cumulative incidences of overall, HBeAg‐reversion and HBeAg‐negative virological relapse were 70.2%, 54%, and 53.5%, respectively. The common factors associated with HBeAg‐reversion and HBeAg‐negative virological relapse were tenofovir treatment (hazard ratio [HR] = 5.411, p < 0.001; HR = 2.066, p = 0.006, respectively) and HBsAg at end of treatment (EOT) (HR = 1.461, p = 0.001; HR = 1.303, p = 0.019, respectively). The 5‐year cumulative incidence of HBsAg loss in SVR patients was 13.7% and EOT HBsAg was the only associated factor (HR = 0.524, p = 0.024). Compared to that of ETV‐treated patients, TDF‐treated patients had a significantly higher 3‐year cumulative incidence of virological relapse (87.3% vs. 62.8%, p < 0.001), earlier HBeAg‐reversion virological relapse (2.9 vs. 7.8 months, p < 0.001), a higher rate of HBeAg‐reversion virological relapse (53.2% vs. 26.7%) and a lower SVR rate (15.6% vs. 39.4%) (p < 0.001). In summary, the clinical outcomes after treatment cessation in HBeAg‐positive patients with HBeAg loss were composed of HBeAg‐reversion virological relapse, HBeAg‐negative virological relapse and SVR. TDF was significantly associated with off‐treatment virological relapse. EOT HBsAg plays an important role in HBsAg loss among SVR patients and posttreatment virological relapse.
Integrative review on career interventions with unemployed people: Nature, outcomes, and recommendations
Authors: de Carvalho Catarina Luzia , Taveira Maria do Céu , Silva Ana Daniela
Published: October 2023

The study of career development among unemployed people is vital for effective institutional responses. This integrative review based on Torraco's protocol fills a literature gap by synthesizing research on interventions for this population. Seven keywords, five databases, and six eligibility criteria were defined. Among 324 articles, 36 were reviewed. Findings highlight diverse counseling modalities, emphasizing group interventions and remote delivery. Tailored approaches, including length, frequency, and social‐emotional and career dimensions, are crucial. Practical recommendations emphasize comprehensive, psychological support, goal‐oriented counseling, and postintervention assistance. These insights underscore vocational psychology's importance in addressing unemployment, impacting government policies, career services, and psychologists.
Confirming the stimulated Raman origin of singlet‐oxygen photogeneration
Authors: Olaizola Aristides Marcano , Zerrad Ameen , Janneto Fahim , Kingsley David H.
Published: October 2023

We confirm the Raman origin of the singlet oxygen photogenerated in water environments without using photosensitizers. Nanosecond light pulses in the blue region of the spectra (405–480 nm) generate Raman Stokes excitation of singlet oxygen in the red region (600–670 nm) when focusing on pure distilled water. The excitation also produces Stokes components corresponding to the stretching modes of water molecules. The time evolution of both types of Stokes components, singlet oxygen, and stretching modes correspond to the time duration of the excitation pulse as expected for a Raman process. Their power dependences are also similar. Finally, both signals exhibit high refractive ring structures due to the nonlinear optical interaction generated by the stimulated Raman process.
Do resected colorectal cancer patients need early chest imaging? Impact of clinicopathologic characteristics on time to development of pulmonary metastases
Authors: Deboever Nathaniel , Bayley Erin M. , Eisenberg Michael A. , Hofstetter Wayne L. , Mehran Reza J. , Rice David C. , Rajaram Ravi , Roth Jack A. , Sepesi Boris , Swisher Stephen G. , Vaporciyan Ara A. , Walsh Garrett L. , Bednarski Brian K. , Morris Van K. , Antonoff Mara B.
Published: October 2023

Background and Objectives

For patients with colorectal cancer (CRC), the lung is the most common extra‐abdominal site of distant metastasis. However, practices for chest imaging after colorectal resection vary widely. We aimed to identify characteristics that may indicate a need for early follow‐up imaging.

Methods

We retrospectively reviewed charts of patients who underwent CRC resection, collecting clinicopathologic details and oncologic outcomes. Patients were grouped by timing of pulmonary metastases (PM) development. Analyses were performed to investigate odds ratio (OR) of PM diagnosis within 3 months of CRC resection.

Results

Of 1600 patients with resected CRC, 233 (14.6%) developed PM, at a median of 15.4 months following CRC resection. Univariable analyses revealed age, receipt of systemic therapy, lymph node ratio (LNR), lymphovascular and perineural invasion, and KRAS mutation as risk factors for PM. Furthermore, multivariable regression showed neoadjuvant therapy (OR: 2.99, p < 0.001), adjuvant therapy (OR: 6.28, p < 0.001), LNR (OR: 28.91, p < 0.001), and KRAS alteration (OR: 5.19, p < 0.001) to predict PM within 3 months post‐resection.

Conclusions

We identified clinicopathologic characteristics that predict development of PM within 3 months after primary CRC resection. Early surveillance in such patients should be emphasized to ensure timely identification and treatment of PM.
Triggered Crosslinking of Main‐Chain Enediyne Polyurethanes via Bergman Cyclization
Authors: Cai Yue , Binder Wolfgang H.
Published: October 2023

Crosslinking chemistries occupy an important position in polymer modification with a particular importance when triggered in response to external stimuli. Enediyne (EDY) moieties are used as functional entities in this work, known to undergo a pericyclic Bergman cyclization (BC) to induce a triggered crosslinking of polyurethanes (PU) via the intermediately formed diradicals. Diamino‐EDYs, where the distance between the enyne‐moieties is known to be critical to induce a BC, are placed repetitively as main‐chain structural elements in isophorone‐based PUs to induce reinforcement upon heating, compression, or stretching. A 7‐day compression under room temperature results in a ≈69% activation of the BC, together with the observation of an increase in tensile strength by 62% after 25 stretching cycles. The occurrence of BC is further proven by the decreased exothermic values in differential scanning calorimetry, together with characteristic peaks of the formed benzene moieties via IR spectroscopy. Purely heat‐induced crosslinking contributes to 191% of the maximum tensile strength in comparison to the virgin PU. The BC herein forms an excellent crosslinking strategy, triggered by heat or force in PU materials.
Manipulating Cis‐Trans Copolymer Chain Conformation to Simultaneously Improve Permittivity and DC Breakdown Strength in Polythiourea
Authors: Jiang Liuhao , Liu Xia , Hu Shichun , Li Mingru , Yang Liuqing , Feng Yang , Li Shengtao
Published: October 2023

Polythioureas (PTUs) show great potentials for applications in the new generation of film capacitors due to their excellent dielectric properties. Herein, the cis‐trans copolymer chain of PTU is successfully tailored by employing cis and trans cyclohexyl spacers. The relationship between the copolymer chain conformation, microstructure, and dielectric properties is carefully explored by a series of analysis. Compared with cis conformation, the trans with less steric hindrance can promote the formation of H‐bonds. The enhanced H‐bonding interactions not only reduce the molecular inter‐chain spacing, but also drive the self‐assembly of molecular chains to form cylindrical and droplet nano‐morphologies. The phase separation between cis and trans PTUs is confirmed by combining the experimental results of TEM and DSC, and the CT64‐PTU with the most two‐phase interface thus obtains the highest permittivity of 5.5 (@10 Hz). The reduced molecular inter‐chain spacing is accompanied by a decreased hopping distance of charges, which improves breakdown strength by 17% from 498 MV/m to 580 MV/m. Therefore, the cis‐trans copolymer chain conformation in PTU provides a simultaneous high permittivity and breakdown strength. This research offers a strategy to further design high‐performance dielectrics via regulation of copolymer chain conformation.
Construction of Carbon Dots@LiCl‐polyacrylamide with Humidity‐Induced Ultralong Room‐Temperature Phosphorescence to Fluorescence and Rigid‐to‐Flexible Transition Behavior
Authors: Zhao Huimin , Jia Xiaoyong , Zhang Man , Zhu Liangliang
Published: October 2023

The continuous advancement of luminescent materials has placed increasingly stringent requirements on dynamic color‐tunable ultralong room‐temperature phosphorescence (URTP) materials that can respond to external stimuli. Nevertheless, endowing URTP materials with stimuli‐response‐induced dynamic color tuning is a challenging task. This study introduces a carbon dots (CDs)@LiCl‐polyacrylamide (PAM) polymer system that switches from URTP to fluorescence under humidity stimuli, accompanied by a transition from rigidity to flexibility. The obtained rigid CDs@LiCl‐PAM exhibits ultralong green phosphorescence with a lifetime of 560 ms in the initial state. After absorbing moisture, it becomes flexible and its phosphorescence switches off. Moreover, the emission of the CDs@LiCl‐PAM film depends on the excitation wavelength. This property can potentially used in multicolored luminescence applications and displays. Moreover, multicolor luminescent patterns can be constructed in situ using the water‐absorption ability of the obtained thin film and the Förster resonance energy‐transfer strategy. The proposed strategy is expected to promote the interdisciplinary development of intelligent information encryption, anti‐counterfeiting, and smart flexible display materials.
Single‐cell sequencing reveals SATB2/NOTCH1 signaling promotes the progression of malignancy of epithelial cells from papillary thyroid cancer
Authors: Zhang Wenqian , Wang Jing , Huang Dongning , Liu Zhu , Lu Tie , Cui Chen , Li Zhendong
Published: October 2023

Although most papillary thyroid cancers (PTCs) are deemed to have a favorable clinical course and outcome, some develop an aggressive biological behavior at diagnosis or during treatment. Single‐cell RNA sequencing (scRNA‐seq), which is based on quantifying the features of individual cells to resolve tumor tissue heterogeneity, was used to uncover gene regulatory relationships and trace the transcriptional trajectories underlying the malignant transformation. In this study, we performed single‐cell sequencing on samples from four PTC patients and one benign thyroid tumor patient. These included two papillary thyroid microcarcinoma cancers (PTMC) patients, two age‐matched advanced PTC patients with invading surrounding tissues, and one patient undergoing surgical treatment due to a benign thyroid tumor. We constructed a new PTC RNA spectrum using single‐cell sequencing. Single‐cell sequencing analysis indicated that there was a highly invasive subgroup in the PTC epithelial cells, the expression of SATB2 (special AT‐rich binding protein‐2) was related to the prognosis and clinical progress of PTC, and SATB2 could promote the proliferation, migration, and invasion of PTC cells. We found that NOTCH1 was the key target gene of SATB2, and the activation of the SATB2/NOTCH1 pathway was one of the reasons for the high carcinogenicity of this subgroup.
Role of epigenetic modifications and aging in inflammatory bowel disease
Authors: Du Yanting , Li Guo , Zhou Yang , Zuo Min , Wang Hu , Liu Yanan , Hong Liquan
Published: October 2023

Inflammatory bowel disease (IBD), which encompasses ulcerative colitis (UC) and Crohn's disease (CD), refers to a chronic and recurrent nonspecific inflammatory condition affecting the mucosal and submucosal layers of the intestines. A positive family history has been identified as a risk factor for the onset of IBD, likely influenced by genetic and environmental factors. In addition to intestinal damage, patients may have extraintestinal manifestations such as inflammation of the skin, eyes, and joints, inflammation of the liver or bile ducts, kidney stones, iron‐deficiency anemia, and growth retardation in children, which may complicate diagnosis and treatment. Therefore, investigating the mechanisms of IBD and finding precise therapeutic targets provides enormous benefits to patients with IBD. Multiple studies have consistently demonstrated the influential role of dietary metabolism and aging in the development of IBD. Moreover, emerging evidence suggests that aging often coincides with alterations in epigenetic modifications, while diet metabolism mediates these epigenetic changes. Epigenetics has emerged as a prospective field for identifying novel biomarkers to facilitate the diagnosis, prognosis, and treatment of diseases. Therefore, in this perspective, we summarize the cross‐talk between epigenetic modifications, diet metabolism, and aging in the pathogenesis of IBD and attempt to identify new potential therapeutic targets and strategies.
Conjoined thoracodorsal perforator‐supercharged dorsal intercostal artery perforator propeller flap for reconstruction of a complex upper back defect: Case report and review of the literature on supercharged pedicled perforator flaps
Authors: Brunetti Beniamino , Salzillo Rosa , De Bernardis Riccardo , Tenna Stefania , Camilloni Chiara , Persichetti Paolo
Published: October 2023

The reported complications' rate of perforator propeller flaps is variably high, but the etiology of distal flap necrosis, potentially linked to vascular insufficiency, is yet to be clarified. Vascular augmentation procedures have been previously described involving an extra anastomosis of a superficial vein, while a perforator‐to‐perforator supercharging approach has been only sporadically documented in literature. We present a case of perforator‐to‐perforator vascular supercharging of an extended dorsal intercostal artery perforator (DICAP) propeller flap to provide a salvage option for pedicled flap complicated by venous congestion. A 71‐year‐old male patient underwent Dermatofibrosarcoma Protuberans resection in the upper back, leading to a 17 × 17 cm defect with bone exposure. A 30 × 9 cm DICAP propeller flap was planned, with the distal third of the flap designed over the adjacent Thoracodorsal artery perforasome, in a conjoined fashion. Considering the small DICAP pedicle caliber and the flap lateral extension, a thoracodorsal artery perforator vein was dissected and included in the distal flap. Once the flap was raised on its main pedicle, the skin paddle turned blue, showing signs of venous insufficiency. Indocyanine green angiography (ICG) showed a viable proximal half of the flap. Hence, after rotating the skin paddle to reach the upper margin of the defect, an additional anastomosis between the perforating thoracodorsal vein and the perforating vein of the dorsal scapular pedicle was performed according to the perforator‐to‐perforator approach. Doing so, both clinical and ICG examinations showed a well perfused flap, with normal capillary refill. The postoperative course was uneventful, and the patient obtained a good oncological and reconstructive result 4 months postoperatively. The second Vasconez law (“all of the flap will survive except the part that you need”) is often encountered in propeller flaps surgery. Our case shows that it is possible to prevent or overcome this problem by planning appropriate vascular augmentation procedures according to the perforator‐to‐perforator approach, being guided by advanced vascular imaging tools like ICG.
A Mediterranean Diet‐Based Metabolomic Score and Cognitive Decline in Older Adults: A Case–Control Analysis Nested within the Three‐City Cohort Study
Authors: Tor‐Roca Alba , Sánchez‐Pla Alex , Korosi Aniko , Pallàs Mercè , Lucassen Paul J. , Castellano‐Escuder Pol , Aigner Ludwig , González‐Domínguez Raúl , Manach Claudine , Carmona Francisco , Vegas Esteban , Helmer Catherine , Feart Catherine , Lefèvre‐Arbogast Sophie , Neuffer Jeanne , Lee Hyunah , Thuret Sandrine , Andres‐Lacueva Cristina , Samieri Cécilia , Urpi‐Sarda Mireia
Published: October 2023

Scope

Evidence on the Mediterranean diet (MD) and age‐related cognitive decline (CD) is still inconclusive partly due to self‐reported dietary assessment. The aim of the current study is to develop an MD‐ metabolomic score (MDMS) and investigate its association with CD in community‐dwelling older adults.

Methods and results

This study includes participants from the Three‐City Study from the Bordeaux (n = 418) and Dijon (n = 422) cohorts who are free of dementia at baseline. Repeated measures of cognition over 12 years are collected. An MDMS is designed based on serum biomarkers related to MD key food groups and using a targeted metabolomics platform. Associations with CD are investigated through conditional logistic regression (matched on age, sex, and education level) in both sample sets. The MDMS is found to be inversely associated with CD (odds ratio [OR] [95% confidence interval (CI)] = 0.90 [0.80–1.00]; p = 0.048) in the Bordeaux (discovery) cohort. Results are comparable in the Dijon (validation) cohort, with a trend toward significance (OR [95% CI] = 0.91 [0.83–1.01]; p = 0.084).

Conclusions

A greater adherence to the MD, here assessed by a serum MDMS, is associated with lower odds of CD in older adults.
Dietary Supplement with Tribulus terrestris L. Extract Exhibits Protective Effects on Ischemic Stroke Rats
Authors: Guo Wenjun , Yang Jingxuan , Wang Jifeng , Xu Xiaohang , Huang Jinghan , Liu Yue , Xie Shengxu , Xu Yajuan
Published: October 2023

Scope

Among herbal dietary supplements, the extract of Tribulus terrestris L. (TT) has been used as a commercially registered product in multiple studies. The previous studies demonstrate the protective effect of gross saponins of TT (GSTTF) on ischemic stroke. However, the mechanism by which GSTTF protects against ischemic stroke is still unclear.

Methods and results

The study applies molecular biology and unbiased transcriptomics to explore the pathways and targets underlying the therapeutic impact of GSTTF in treating ischemic stroke. The mRNA of brain tissues from different groups is analyzed using a transcriptomics method. The data reveal that treatment with GSTTF significantly reduces elevated CRP, IL‐6, and Ca2+ levels induced by middle cerebral artery occlusion (MCAO). A total of 61 differentially expressed genes (DEGs) are identified, GSTTF is found to effectively reverse the abnormal mRNA expression levels in rat brain tissues affected by ischemic stroke models. These positive effects of GSTTF are likely achieved through the suppression of calcium ion and the MyD88/IKK/NF‐κB signaling pathway.

Conclusions

This study uncovers the mechanisms behind the efficacy of GSTTF in treating ischemic stroke, which not only expands its potential medicinal applications but also confirmed its potential as a dietary supplement.
Signal‐difference‐to‐noise comparison of temporal subtraction, kV‐switching dual‐energy and photon‐counting dual‐energy x‐ray angiography
Authors: Aubert Sarah , Tanguay Jesse
Published: October 2023

Background

Dual‐energy (DE) x‐ray angiography with photon‐counting detectors (PCDs) may enable single‐exposure DE imaging of coronary vasculature.

Purpose

To compare the iodine signal‐difference‐to‐noise ratio (SDNR) of single‐exposure DE angiography with digital subtraction angiography (DSA) and kV‐switching DE angiography for matched patient x‐ray exposure.

Methods

In a phantom study, we determined the technique parameters that maximized the iodine SDNR per root entrance air kerma for DSA, kV‐switching DE angiography and single‐exposure DE angiography. We measured SDNR from images of a phantom consisting of an iodine step‐wedge immersed in a water tank of either 20  or 30 cm in thickness. We also imaged a phantom with simulated vessels embedded in background clutter and measured vessel SDNR. For this second phantom, we also applied anti‐correlated noise reduction (ACNR) and calculated the resulting iodine SDNR. All images were acquired using a cadmium telluride PCD with two energy bins and analog charge summing for charge sharing suppression. The energy‐discrimination capabilities were only used for the single‐exposure DE approach. Optimized techniques were compared in terms of SDNR per root air kerma for two levels of x‐ray scatter.

Results

For the same patient x‐ray exposure, the SDNR of single‐exposure DE imaging without ACNR was 75% to 85% of that of kV‐switching DE imaging (also without ACNR) and DSA, the latter two of which had nearly equal SDNR. The single‐exposure DE approach required ∼50% of the tube load of the kV‐switching approach to achieve the same SDNR. For matched patient air kermas, the single exposure approach required only ∼25% of the tube load of the kV‐switching approach. ACNR increased SDNR by 2.4 and 3.0 for kV‐switching and single‐exposure DE imaging, respectively.

Conclusions

Photon‐counting, single‐exposure DE angiography can suppress soft tissues and provide iodine SDNR levels comparable to DSA and kV‐switching DE angiography for matched patient radiation exposures. When ACNR is used to reduce DE image noise, the SDNR of single‐exposure DE imaging and kV‐switching DE imaging exceed that of DSA by more than a factor of two. Compared to kV‐switching DE imaging, single‐exposure DE imaging requires substantially lower tube loading to achieve the same SDNR.
An optimized DEM‐SPH model for surge waves induced by riverside landslides
Authors: Li Yang , Liu Hong‐Qing , Yang Lei , Liu Yong
Published: October 2023

Riverside landslides can induce surge waves during the process of entering water. The landslide‐induced surge wave is often regarded as a significant secondary disaster, as its impact region is likely to be even more remarkable than the landslide itself. Due to the large deformation of the soil landslide and water body during the evolution of surge waves, commonly adopted multi‐phase flow models and mesh‐based methods coupled with discrete element models have some limitations, such as weak accuracy, and simulation distortion with immature coupling algorithms. As a result, the pure meshless method of smoothed particle hydrodynamics (SPH) coupling discrete element methods (DEM) become promising. Modified from the traditional empirical formulae‐based coupling algorithm, this study proposes a semi‐resolved algorithm that effectively eliminates the particle distortion at the fluid‐solid coupling interface. The proposed model demonstrates its superiority through a comparison of the pressure and porosity near the coupling interface. Furthermore, the optimized DEM‐SPH model is applied to simulate landslide‐induced surge waves, and the simulation results have also validated the accuracy of the model. This model is capable of accurately simulating the entire propagation process from landslide entry into water to the wave reaching the opposite shore, and therefore provides an effective tool for the prediction and mitigation of wave hazards caused by landslides.
Beyond the urothelium: Interplay between autonomic nervous system and bladder inflammation in urinary tract infection, bladder pain syndrome with interstitial cystitis and neurogenic lower urinary tract dysfunction in spinal cord injury—ICI‐RS 2023
Authors: Wyndaele Michel , Charrua Ana , Hervé François , Aronsson Patrik , Grundy Luke , Khullar Vik , Wein Alan , Abrams Paul , Cruz Francisco , Cruz Célia Duarte
Published: October 2023

Introduction

Inflammation and neuronal hypersensitivity are reactive protective mechanisms after urothelial injury. In lower urinary tract dysfunctions (LUTD), such as urinary tract infection (UTI), bladder pain syndrome with interstitial cystitis (BPS/IC) and neurogenic LUTD after spinal cord injury (SCI), chronic inflammation can develop. It is unclear how the protective reactionary inflammation escalates into chronic disease in some patients.

Methods

During its 2023 meeting in Bristol, the International Consultation on Incontinence‐Research Society (ICI‐RS) reviewed the urothelial and inflammatory changes after UTI, BPS/IC and SCI. Potential factors contributing to the evolution into chronic disease were explored in a think‐tank.

Results

Five topics were discussed. (1) Visceral fat metabolism participates in the systemic pro‐inflammatory effect of noradrenalin in BPS/IC and SCI. Sympathetic nervous system‐adipocyte‐bladder crosstalk needs further investigation. (2) Sympathetic hyperactivity also potentiates immune depression in SCI and needs to be investigated in BPS/IC. Gabapentin and tumor necrosis factor‐α are promising research targets. (3) The exact peripheral neurons involved in the integrative protective unit formed by nervous and immune systems need to be further identified. (4) Neurotransmitter changes in SCI and BPS/IC: Neurotransmitter crosstalk needs to be considered in identifying new therapeutic targets. (5) The change from eubiosis to dysbiosis in SCI can contribute to UTI susceptibility and needs to be unraveled.

Conclusions

The think‐tank discussed whether visceral fat metabolism, immune depression through sympathetic hyperactivity, peripheral nerves and neurotransmitter crosstalk, and the change in microbiome could provide explanations in the heterogenic development of chronic inflammation in LUTD. High‐priority research questions were identified.
Crystal Modifications of a Cyclic Guanosine Phosphorothioate Analogue, a Drug Candidate for Retinal Neurodegenerations
Authors: Pérez Oswaldo , Schipper Nicolaas , Leandri Valentina , Svensson Per H. , Bohlin Martin , Loftsson Thorsteinn , Bollmark Martin
Published: October 2023

In contribution to the pharmaceutical development of cyclic guanosine monophosphorothioate analogue cGMPSA as a potential active pharmaceutical ingredient (API) for the treatment of inherited retinal degenerations (IRDs), its neutral form (cGMPSA‐H) and salts of sodium (‐Na), calcium (‐Ca), ammonium (‐NH4), triethylammonium (‐TEA), tris(hydroxymethyl)aminomethane (‐Tris), benethamine (‐Bnet), and benzathine (‐BZ) were prepared. Their solid‐state properties were studied with differential scanning calorimetry, thermogravimetric analysis, hot‐stage microscopy, and dynamic vapor sorption, and their solubilities were measured in deionized H2O as well as aqueous HCl and NaOH buffers. A total of 21 crystal modifications of cGMPSA were found and characterized by X‐ray powder diffraction. Despite their crystalline character, no API forms featured any observable melting points during thermal analyses and instead underwent exothermic decomposition at ≥163 °C. Both the vapor sorption behavior and solubility were found to differ significantly across the API forms. cGMPSA‐BZ featured the lowest aqueous solubility and hygroscopicity, with 50 μg/mL and 5 % mass gain at maximum relative humidity. The synthesis and crystallization of some crystal modifications were upscaled to >10 g. Single crystal X‐ray diffraction was performed which resulted in the first crystal structure determination and absolute configuration of a cyclic guanosine monophosphorothioate, confirming the RP‐ conformation at the phosphorus atom.
Physical capacity in children and adolescents with newly diagnosed cancer: A systematic review and meta‐analysis
Authors: Schmidt‐Andersen Peter , Stage Anna , Pouplier Anna , Bastholm Louise H. , Müller Klaus G. , Larsen Anders , Ness Kirsten K. , Larsen Hanne B. , Christensen Jan , Fridh Martin K.
Published: October 2023

Objective

To review the body of evidence on cardiorespiratory fitness, muscle strength, and physical performance in children with newly diagnosed cancer, five databases (MEDLINE, Embase, CINAHL, CENTRAL, and Web of Science) were searched on December 19, 2022.

Methods

Thirteen studies, embodying 594 participants within 1 month of cancer diagnosis and 3674 healthy controls were included. Eighteen different outcomes on cardiorespiratory fitness (n = 2), muscle strength (n = 5), physical performance (n = 10), and adverse events (n = 1) were analyzed.

Results

Fifteen out of 17 outcomes on physical capacity showed severe impairments compared with healthy controls. Where possible, random‐effects meta‐analysis was conducted to synthesize the results. No adverse events were reported related to testing.

Conclusion

Children with cancer have impaired cardiorespiratory fitness, muscle strength, and physical performance within the first month after diagnosis. However, the evidence is based on a small number of studies with large clinical heterogeneity, limiting the certainty of evidence.
Stratified analysis in comparative effectiveness studies that emulate randomized trials
Authors: Htoo Phyo T. , Glynn Robert J. , Wang Shirley , Paik Julie M. , Schneeweiss Sebastian , Walker Alexander M. , Patorno Elisabetta
Published: October 2023

Purpose

For observational cohort studies that employ matching by propensity scores (PS), preliminary stratification by consequential predictors of outcome better emulates stratified randomization and potentially reduces variance and bias through relaxed dependence on modeling assumptions. We assessed the impact of pre‐stratification in two real‐life examples. For both, prior evidence from placebo‐controlled randomized clinical trials (RCTs) suggested small or no risk reduction, but observational analysis suggested protection, presumably the result of confounding bias.

Study Design and Setting

The study populations consisted of Medicare beneficiaries (2014‐18) with type 2 diabetes initiating either (i) empagliflozin versus dipeptidyl peptidase‐4 inhibitors (DPP‐4i) or (ii) empagliflozin versus glucagon‐like peptide‐1 receptor agonists (GLP‐1RA). The outcome was myocardial infarction or stroke. We estimated hazard ratios (HR) and rate differences (RD) after controlling for 143 pre‐exposure covariates via 1:1 PS matching after (1) PS estimation in the total cohort (total‐cohort PS‐matching) and (2) PS estimation separately by baseline cardiovascular disease (stratified PS matching).

Results

Stratified PS matching resulted in HRs that exceeded those from total‐cohort PS‐matching by 13% and 9%, respectively, for the comparisons of empagliflozin to DPP‐4i and GLP‐1RA. Against both comparators, HRs and RDs after stratified PS matching were closer to the null, with slightly higher variances (2%–3%) than those after total‐cohort PS matching.

Conclusion

Stratified PS matching produced effect estimates closer to the expected trial findings than total‐cohort PS matching. The price paid in increased variance was minimal.
Improvement of thermo‐mechanical and dielectric properties of poly(lactic acid) and thermoplastic polyurethane blend composites using a graphene and BaTiO3 filler
Authors: Wondu Eyob , Kim Jooheon
Published: October 2023

This study focuses on the development of composite materials using thermoplastic polyurethane (TPU) and poly(lactic acid) (PLA) with fillers such as barium titanate (BaTiO3) and graphene. Suitable surface treatment of filler particles is applied to activate the fillers to enhance the compatibility between the fillers and polymer matrix. Specifically, the BaTiO3 particles are hydroxylated and treated with glycidyl methacrylate (GMA), which acts as a compatibilizer between the two matrix polymers. On the other hand, the graphene particles are hydroxylated and treated with isophorone diisocyanate (IPDI), which reacts with the TPU soft segment chains during composite fabrication. The composite samples are fabricated via melt‐blending at 190°C, followed by mini molding at the same operating temperature for subsequent analysis. The results demonstrate a three‐fold improvement in the dielectric constant of 40 wt.% BaTiO3 and graphene–TPU–PLA blends composites relative to that of the neat TPU, along with an improved tensile strength. The tensile strength improvement is attributed to the support of the TPU matrix against the low ductility of the PLA. The thermal conductivity was doubled as compared with the neat TPU–PLA matrix for the 40 wt.% BaTiO3 and graphene–TPU–PLA blends.

Highlights

Composites of TPU–PLA–graphene and BaTiO3 filler particles were fabricated.

The melt blending technique was employed to fabricate the composite.

The dielectric constant was analyzed at both constant and variable frequencies.

Thermal conductivity was doubled (40 [graphene + BaTiO3])
Diagnostic yield of bronchoscopy in children with leukemia or post hematopoietic stem cell transplant
Authors: Georgescu Livia , Rahrig April L. , Montgomery Gregory , Rowan Courtney M.
Published: October 2023

Background

The utility of bronchoscopy with bronchoalveolar lavage (BAL) in immunocompromised children is not well understood. We aim to describe the bronchoscopy diagnostic yield and complications and to investigate factors associated with diagnostic yield.

Methods

This is a single‐center, retrospective cohort study of 60 children with leukemia or post‐hematopoietic stem cell transplant who had a bronchoscopy with BAL between 2017 and 2021. Comparisons were done with regression analysis.

Results

Of the 60 bronchoscopies performed, 46 (77%) revealed diagnostic information: 39 (65%) identified a pathogen, 14 (23.3%) found secretions/mucus plugging, and 6 (10%) found pulmonary hemorrhage. BAL results changed antimicrobial therapy in 27 (45%) cases. Bronchoscopies were performed in the intensive care unit (27/60) or operating room (33/60), with the former having a higher diagnostic yield (96% vs. 60%, p = 0.001). Half (50%) of bronchoscopies found a new infectious diagnosis. Respiratory symptoms (n = 58, 97%), supplemental oxygen use (n = 39, 65%), and antibiotic use (n = 56, 93%) before bronchoscopy were all common. The median volume of fluid instilled during bronchoscopy was 1.3 mL/kg (interquatile range [IQR]: 0.7, 2.6). None of these factors were associated with the diagnostic yield. Complications were rare and minor with only one child having self‐resolved bleeding and four children, previously in room air requiring a nasal cannula. For the 27 (45%) children on mechanical ventilation when the bronchoscopy was performed, there was no difference in ventilator settings pre‐ and post‐bronchoscopy.

Conclusion

Bronchoscopies with BAL are useful, safe, and important in the diagnostic management of pulmonary complications in this cohort of children.
Electrochemical determination of insensitive munition constituents 3‐nitro‐1,2,4‐triazol‐5‐one (NTO) using gold nanoparticle/carbon nanotube‐modified pencil graphite electrode in groundwater sample
Authors: Aslan Nazife , Şen Nilgün , Tecİman İrem , Ali Güngör Mustafa
Published: October 2023

For the electrochemical detection of nitrotriazolone (NTO), multiwalled carbon nanotubes (MWCNT) and gold nanoparticles have been combined to generate nanocomposites. Electrochemical analysis and surface characterisation using scanning electron microscopy (SEM) and energy dispersive X‐ray (EDX) spectroscopy techniques were used to confirm the presence of gold nanoparticles on MWCNT. The electrochemical behavior of NTO at the modified pencil graphite electrode in the pH range of 2.0–10.0 (0.04 M Britton‐Robinson buffer solution) was evaluated using cyclic (CV) and differential pulse voltammetry (DPV).

The suggested electrochemical sensor displayed a quick reaction to NTO with an optimal set of experimental parameters, a linear calibration curve spanning 30 to 1500 nM, and a detection limit of 22.6 nM. Using the differential pulse voltammetry technique, the usefulness of the MWCNT/AuNPs, and PGE for the determination of NTO in groundwater was evaluated.
The activated complement pathway in the fibrous process of benign prostatic hyperplasia
Authors: Hata Junya , Matsuoka Kanako , Akaihata Hidenori , Meguro Satoru , Honda‐Takinami Ruriko , Onagi Akifumi , Koguchi Tomoyuki , Sato Yuichi , Kataoka Masao , Uemura Motohide , Kojima Yoshiyuki
Published: October 2023

Background

To elucidate the changes in activated complement pathway in the fibrous process of benign prostatic hyperplasia (BPH), we analyzed the correlation between complement component expression and histological types of fibrosis using human BPH tissue.

Methods

Fifty‐six histological BPH patients who underwent prostate needle biopsy at our institution (mean age 68.6 ± 6.5 years), divided into two histological groups, fibromuscular and fibrous, were compared. Inflammatory cell infiltration in BPH tissue was evaluated by immunohistochemical staining using CD45, with complement expression analysis performed using C3, factor B, and C5b‐9 antibody, and the occupancy ratio of the stained region was calculated. Further, correlation between the histological types of fibrous components in BPH tissue and lower urinary tract symptoms questionnaires was analyzed.

Results

Twenty‐seven (48.2%) and 29 (51.8%) cases were classified in the fibromuscular and fibrous groups, respectively. The proportion of CD45‐positive cells in BPH tissue was significantly higher in the fibromuscular group. In complement component analysis, factor B did not significantly differ between groups, while C3 (fibromuscular group; 10.7 ± 8.2%, fibrous group; 16.4 ± 12.7%) and C5b‐9 (fibromuscular group; 15.9 ± 6.2%, fibrous group; 17.6 ± 9.2%) were significantly higher in the fibrous group (p = 0.04, p = 0.04, respectively). International Prostate Symptom Score Q5 subscore, indicating slow stream, was significantly higher in the fibrous group (p = 0.04).

Conclusions

In fibrous BPH with abundant fibrosis, the late complement pathway in addition to alternative pathway was activated compared to fibromuscular BPH. These results suggested that the alternative and late complement pathways were involved in the histological fibrous process of BPH.
Assessment of three‐dimensional RNA structure prediction in CASP15
Authors: Das Rhiju , Kretsch Rachael C. , Simpkin Adam J. , Mulvaney Thomas , Pham Phillip , Rangan Ramya , Bu Fan , Keegan Ronan M. , Topf Maya , Rigden Daniel J. , Miao Zhichao , Westhof Eric
Published: October 2023

The prediction of RNA three‐dimensional structures remains an unsolved problem. Here, we report assessments of RNA structure predictions in CASP15, the first CASP exercise that involved RNA structure modeling. Forty‐two predictor groups submitted models for at least one of twelve RNA‐containing targets. These models were evaluated by the RNA‐Puzzles organizers and, separately, by a CASP‐recruited team using metrics (GDT, lDDT) and approaches (Z‐score rankings) initially developed for assessment of proteins and generalized here for RNA assessment. The two assessments independently ranked the same predictor groups as first (AIchemy_RNA2), second (Chen), and third (RNAPolis and GeneSilico, tied); predictions from deep learning approaches were significantly worse than these top ranked groups, which did not use deep learning. Further analyses based on direct comparison of predicted models to cryogenic electron microscopy (cryo‐EM) maps and x‐ray diffraction data support these rankings. With the exception of two RNA‐protein complexes, models submitted by CASP15 groups correctly predicted the global fold of the RNA targets. Comparisons of CASP15 submissions to designed RNA nanostructures as well as molecular replacement trials highlight the potential utility of current RNA modeling approaches for RNA nanotechnology and structural biology, respectively. Nevertheless, challenges remain in modeling fine details such as noncanonical pairs, in ranking among submitted models, and in prediction of multiple structures resolved by cryo‐EM or crystallography.