bluuebunny/crossref_metadata_2025 huggingface dataset:
Dysphagia screening post-stroke: systematic review
Authors: Mancin Stefano , Sguanci Marco , Reggiani Francesco , Morenghi Emanuela , Piredda Michela , De Marinis Maria Grazia
Published: June 2023

Background/scope

Stroke is one of the main causes of death, especially when associated with dysphagia. Hence, the assessment of nutritional status and aspiration risk is important to improve clinical outcomes. The aim of this systematic review is to identify which are the most suitable dysphagia screening tools in chronic post-stroke patients.

Methodology

A systematic literature search was conducted for articles published from 1 January 2000 to 30 November 2022 in the Cochrane Library, PubMed, Embase, CINAHL, Scopus and Web of Science databases, including primary studies providing quantitative or qualitative data. Additionally, a manual search was conducted scanning the reference lists of relevant articles and Google Scholar was searched to retrieve additional records. The process of screening, selection and inclusion of the articles, as well as the assessment of risk of bias and methodological quality, were conducted by two reviewers.

Results

Out of the 3672 records identified, we included 10 studies, mostly (n=9) cross-sectional, evaluating screening for dysphagia in 1653 chronic post-stroke patients. Volume-Viscosity Swallow Test was the only test applied in multiple studies with adequate sample size, demonstrating high diagnostic accuracy (sensitivity=96.6%–88.2%; specificity=83.3%–71.4%) compared with the videofluoroscopic swallowing study.

Conclusions

Dysphagia is an important complication in chronic post-stroke patients. Early identification of this condition through screening tools with adequate diagnostic accuracy is of paramount importance. The limited number of studies available and their small sample sizes may be a limitation to this study.

PROSPERO registration number

CRD42022372303.
Role of vanishing complexity factor in generating spherically symmetric gravitationally decoupled solution for self-gravitating compact object
Authors: Maurya S. K. , Errehymy Abdelghani , Dayanandan B. , Ray Saibal , Al-Harbi Nuha , Abdel-Aty Abdel-Haleem
Published: June 2023

In this work, we study the role of the vanishing complexity factor in generating self-gravitating compact objects under gravitational decoupling technique in f(Q)-gravity theory. To tackle the problem, the gravitationally decoupled action for modified f(Q) gravity has been adopted in the form $${\mathscr {S}}={{\mathscr {S}}_{Q}}+{{\mathscr {S}}^{*}_{\theta }}$$

S
=

S
Q

+

S

θ

∗

, where $${\mathscr {S}}_Q$$

S
Q

denotes the Lagrangian density of the fields which appears in the f(Q) theory while $${\mathscr {S}}^{*}_{\theta } (=\alpha {\mathscr {S}}_{\theta }$$

S

θ

∗

(
=
α

S
θ

, where $$\alpha $$
α
is just a coupling parameter which controls the deformation) describes the Lagrangian density for a new kind of gravitational sector which has not been included in f(Q) gravity. After that, we developed an important relation between gravitational potentials via a systematic approach (Contreras and Stuchlik in Eur Phys J C 82:706, 2022) using the vanishing complexity factor condition in the context of f(Q) theory. We have used the Buchdahl model along with the mimic-to-density constraints approach for generating the complexity-free anisotropic solution. The qualitative physical analysis has been done along with the mass-radius relation for different compact objects via $$M-R$$

M
-
R

curves to validate our solution. It is noticed that the coupling constant $$\beta _1$$

β
1

has a definite impact on constraining the mass and radii of the object that are shown in $$M-R$$

M
-
R

curves. The obtained results show that the compactness of the objects can be controlled by the coupling parameters.
Anti-icing of solid surfaces based on droplet dynamics
Authors: Zhang Kaixuan , Li Jie , Wang Yulei , Lin Chensen , Zhao Jiayi , Liu Yang , Chen Shuo
Published: June 2023

Anti-icing is a crucial concern for solid surfaces in numerous industrial domains and has garnered significant attention in recent years. Traditional anti-icing methods for solid surfaces often require a substantial input of energy. In this study, we provide a brief overview of the potential applications of anti-icing and recent advancements in the field. Then, we present a novel anti-icing method, the design of superhydrophobic anti-icing surfaces based on droplet dynamics. Additionally, we delve into several related topics that could benefit future research in the area, such as the design of solid surfaces with various bio-inspired properties, among others.
A ventilation barrier for low-frequency sound insulation
Authors: Chu Jiaming , Liang Xiao , Yang Qifu , Ouyang Xiangjun , Su Liang , Liang Haofeng , Yang Zhen , Chen Tao , Wang Wenjie
Published: June 2023

This paper proposes a ventilation barrier for low-frequency sound insulation with a double-opening Helmholtz’s periodic structure. The energy band characteristics of the unit structure and the sound transmission loss of the ventilation barrier are calculated using the finite element method. The research results show that the ventilation barrier exhibits excellent sound insulation in the range of 323–803[Formula: see text]Hz, and the sound insulation band is consistent with the bandgap of the unit structure. In order to reveal the sound insulation mechanism, we have performed a modal analysis of the unit structure. Further, the effects of different dimensional parameters on the structural bandgap are analyzed by changing the structure. The results show that extending the length of the structure inlet or outlet can effectively reduce the start frequency of the low-frequency bandgap, thus achieving the regulation of the sound insulation band. The proposed low-frequency sound insulation ventilation barrier has a simple structure with great application prospects. In addition, the proposed ventilation barrier provides a new idea for noise control in low-frequency ventilation environments.
BILATERAL INSUFFICIENCY FRACTURES OF MEDIAL MALLEOLI IN AN ELDERLY PATIENT: A CASE REPORT
Authors: Kim Seong-Tae , Yoon Euisun , Lee Sungho
Published: June 2023

Insufficiency fractures (IFs) are a type of stress fractures that most commonly occur in the pelvis, followed by the proximal femur and vertebra. Less commonly, the lower leg and foot are involved. However, reports of IF of the medial malleolus are relatively rare. We herein report and discuss a case of bilateral IFs of medial malleoli in an elderly patient who was successfully treated conservatively. To the best of our knowledge, this is the first described case of bilaterally involved insufficiency fractures of medial malleoli.
The relationship between cervical spine range of motion and postural sway in mechanical neck pain: A cross-sectional study
Authors: Vishal Kavitha , Walkay Ashwini , Teo Huixin , Bhat Veena Suresh , Neelapala Y. V. Raghava
Published: June 2023

Background: Impairments in postural sway have been identified in people with mechanical neck pain. The influence of cervical spine range of motion (ROM) on postural sway is unclear in mechanical neck pain (MNP).

Objective: This study investigated the relationship between cervical spine range of motion (ROM) and postural sway in MNP.

Methods: The cervical ROM was measured using the Cervical Range of Motion (CROM) device. Standing postural sway characterised by mean centre of pressure (COP) measurements in the anterior posterior (AP) and medio-lateral direction with eyes closed and feet together condition was recorded on a posturography platform. Pearson product moment correlation coefficient was used to identify the relationship between cervical ROM and postural sway.

Results: Seventy-two MNP individuals (Mean age: [Formula: see text]) of either sex (Male: [Formula: see text]) were recruited. Overall, no statistically significant correlations were identified between cervical spine ROM in sagittal and frontal plane and postural sway (r values ranging from 0.00 to [Formula: see text]; p-values [Formula: see text]). However, a weak negative correlation was present between the cervical rotation and AP (r-[Formula: see text]; p-[Formula: see text]) and mediolateral (r-[Formula: see text]; p-[Formula: see text]) COP excursion.

Conclusion: The cervical spine ROM was found to have a weak relationship with postural sway in individuals with MNP. This suggests the investigation of other mechanisms especially muscle tension which might be responsible for altered postural sway in MNP.
Older than you think: using U–Pb calcite geochronology to better constrain basin-bounding fault reactivation, Inner Moray Firth Basin, western North Sea
Authors: Tamas A. , Holdsworth R. E. , Tamas D. M. , Dempsey E. D. , Hardman K. , Bird A. , Roberts N. M. W. , Lee J. , Underhill J. R. , McCarthy D. , McCaffrey K. J. W. , Selby D.
Published: June 2023

Like many rift basins worldwide, the Inner Moray Firth Basin (IMFB) is bounded by major reactivated fault zones, including the Helmsdale Fault and the Great Glen Fault (GGF). The Jurassic successions exposed onshore close to these faults at Helmsdale and Shandwick preserve folding, calcite veining and minor faulting consistent with sinistral (Helmsdale Fault) and dextral (GGF) transtensional movements. This deformation has been widely attributed to Cenozoic post-rift fault reactivation. Onshore fieldwork and U–Pb calcite geochronology of five vein samples associated with transtensional movements along the Helmsdale Fault and a splay of the GGF show that faulting occurred during the Early Cretaceous (
c.
128–115 Ma, Barremian–Aptian), while the Helmsdale Fault preserves evidence for earlier Late Jurassic sinistral movements (
c.
159 Ma, Oxfordian). This demonstrates that both basin-bounding faults were substantially reactivated during the episodic NW–SE-directed Mesozoic rifting that formed the IMFB. Although there is good evidence for Cenozoic reactivation of the GGF offshore, the extent of such deformation along the north coast of the IMFB remains uncertain. Our findings illustrate the importance of oblique-slip reactivation processes in shaping the evolution of continental rift basins given that this deformation style may not be immediately obvious in interpretations of offshore seismic reflection data.

Supplementary Material:
Appendix A – orthomosaic model obtained from unmanned aerial vehicle (UAV) photography of the Helmsdale locality (GeoTiff format); Appendix B – orthomosaic model obtained from UAV photography of the Shandwick locality (GeoTiff format); Appendix C – geochronology data; and Appendix D – additional thin section microphotographs of sample HD1 showing repeated cycles of syntaxial grain growth are available at
https://doi.org/10.6084/m9.figshare.c.6708518
On the Different Perspectives of Management in Software Engineering Education and their Implications
Authors: Kamthan Pankaj
Published: June 2023

In light of the significance of software to society and of software engineering to industry, this note approaches software engineering education from multiple perspectives of management. These perspectives are salient, but are not necessarily mutually exclusive, and occur commonly in teaching and learning. In doing so, it also considers a renewed understanding of these perspectives brought upon by a 'revitalization' of e-learning during and after the COVID-19 pandemic.
An Interview with John Grundy - 2023 SIGSOFT Awardee
Authors: Soldani Jacopo
Published: June 2023

John Grundy received the 2023 SIGSOFT Distinguished Service Award for continued outstanding service to the software engineering community, including the repeated successful organization of flagship conferences, and leadership in the Australasian research and education community. He received a Ph.D. in computer science from the University of Auckland (New Zealand), and he is currently Australian Laureate Fellow and Professor of Software Engineering at Monash University. Beyond this, John Grundy is also Fellow of Automated Software Engineering, Fellow of Engineers Australia, Certified Professional Engineer, Engineering Executive, Senior Member of the ACM and Senior Member of the IEEE.
Deep Spatial Prediction via Heterogeneous Multi-source Self-supervision
Authors: Zhang Minxing , Yu Dazhou , Li Yun , Zhao Liang
Published: June 2023

Spatial prediction is to predict the values of the targeted variable, such as PM2.5 values and temperature, at arbitrary locations based on the collected geospatial data. It greatly affects the key research topics in geoscience in terms of obtaining heterogeneous spatial information (e.g., soil conditions, precipitation rates, wheat yields) for geographic modeling and decision-making at local, regional, and global scales. In situ data, collected by ground-level in situ sensors, and remote sensing data, collected by satellite or aircraft, are two important data sources for this task. In situ data are relatively accurate while sparse and unevenly distributed. Remote sensing data cover large spatial areas, but are coarse with low spatiotemporal resolution and prone to interference. How to synergize the complementary strength of these two data types is still a grand challenge. Moreover, it is difficult to model the unknown spatial predictive mapping while handling the tradeoff between spatial autocorrelation and heterogeneity. Third, representing spatial relations without substantial information loss is also a critical issue. To address these challenges, we propose a novel Heterogeneous Self-supervised Spatial Prediction (HSSP) framework that synergizes multi-source data by minimizing the inconsistency between in situ and remote sensing observations. We propose a new deep geometric spatial interpolation model as the prediction backbone that automatically interpolates the values of the targeted variable at unknown locations based on existing observations by taking into account both distance and orientation information. Our proposed interpolator is proven to both be the general form of popular interpolation methods and preserve spatial information. The spatial prediction is enhanced by a novel error-compensation framework to capture the prediction inconsistency due to spatial heterogeneity. Extensive experiments have been conducted on real-world datasets and demonstrated our model’s superiority in performance over state-of-the-art models.
A Computer Vision-Based System for Recognition and Classification of Urdu Sign Language Dataset for Differently Abled People Using Artificial Intelligence
Authors: Zahid Hira , Syed Sidra Abid , Rashid Munaf , Hussain Samreen , Umer Asif , Waheed Abdul , Nasim Shahzad , Zareei Mahdi , Mansoor Nafees
Published: June 2023

Communication between normal people and deaf people is the most difficult part of daily life worldwide. It is difficult for a normal person to understand a word from the deaf one in their daily routine. So, to communicate with deaf people, different countries developed different sign languages to make communication easy. In Pakistan, for deaf people, the government developed Urdu Sign Language to communicate with deaf people. Physical trainers and experts are difficult to provide everywhere in society, so we need such a computer/mobile-based system to convert the deaf sign symbol into voice and written alphabet that the normal person can easily get the intentions of the deaf one. In this paper, we provided an image processing and deep learning-based model for Urdu Sign Language. The proposed model is implemented in Python 3 and uses different image processing and machine techniques to capture the video and transform the symbols into voice and Urdu writing. First, we get a video from the deaf person, and then the model crops the frames into pictures. Then, the individual picture is recognized for the sign symbol such as if the deaf showed a symbol for one, then the model recognizes it and shows the letter which he/she wants to tell. Image processing techniques such as OpenCV are used for image recognition and classification while TensorFlow and linear regression are used for training the model to behave intelligently in the future. The results show that the proposed model increased accuracy from 80% to 97% and 100% accordingly. The accuracy of the previously available work was 80% when we implemented the algorithms, while with the proposed algorithm, when we used linear regression, we achieved the highest accuracy. Similarly, when we used the TensorFlow deep learning algorithm, we achieved 97% accuracy which was less than that of the linear regression model.
Testing the Ability of Teachers and Students to Differentiate between Essays Generated by ChatGPT and High School Students
Authors: Waltzer Tal , Cox Riley L. , Heyman Gail D.
Published: June 2023

The release of ChatGPT in late 2022 prompted widespread concern about the implications of artificial intelligence for academic integrity, but thus far there has been little direct empirical evidence to inform this debate. Participants (69 high school teachers, 140 high school students, total

N
=
209

) took an AI Identification Test in which they read pairs of essays—one written by a high school student and the other by ChatGPT—and guessed which was generated by the chatbot. Accuracy was only 70% for teachers, and it was slightly worse for students (62%). Self-reported confidence did not predict accuracy, nor did experience with ChatGPT or subject-matter expertise. Well-written student essays were especially hard to differentiate from the ChatGPT texts. In another set of measures, students reported greater optimism than their teachers did about the future role of ChatGPT in education. Students expressed disapproval of submitting ChatGPT-generated essays as one’s own but rated this and other possible academic integrity violations involving ChatGPT less negatively than teachers did. These results form an empirical basis for further work on the relationship between AI and academic integrity.
Evaluation of Single-Shade Composite Resin Color Matching on Extracted Human Teeth
Authors: Cruz da Silva Erika Thaís , Charamba Leal Caroline de Farias , Miranda Samille Biasi , Evangelista Santos Mariana , Saeger Meireles Sônia , Maciel de Andrade Ana Karina , Japiassú Resende Montes Marcos Antonio
Published: June 2023

Introduction. Universal single-shade composite resins are characterized by a property that enables the creation of restorations that mimic tooth structure to the extent possible with fewer shades of color. Objectives. This study aimed to instrumentally and visually evaluate the color correspondence of two single-shade composite resins in extracted human teeth multishade composite resins. Methods. Upper central incisors and upper and/or lower molars with intact buccal surfaces were selected. The study consisted of a control group (n = 20): Z250 XT (3M ESPE) (G1) multishade composite resin in colors A1 to A4, and a test group (n = 20) divided further into two equal groups, consisting of single-shade composite resin Omnichroma (Tokuyama Dental) (G2) and single-shade composite resin Vittra APS Unique from (FGM) (G3). Instrumental evaluation was performed using a spectrophotometer, and visual evaluation was performed by three observers. Descriptive measurements related to the differences in color obtained through instrumental means were analyzed using mean and standard deviation, wherein the means were compared using ANOVA, applying the Bonferroni post hoc test. Results. A statistically significant difference was observed among the groups (G1, G2, and G3) (ANOVA:

p
<
0.001

). For the visual assessment, regardless of the assessment group, 77.49% of the teeth were within the acceptable color-match classification, with the single-shade resins showing better correspondence than the multishade resins. Conclusion. Single-shade composite resins showed different color-matching results when compared to multishade resins, both in spectrophotometry and visual evaluations. Clinical Significance. Single-shade composite resins simplify the shade-selection process and are promising materials for use in dental practice.
The Efficacy and Safety of a Low‐Fluence 1064 nm Picosecond ND‐YAG Laser Compared with Those of a Low‐Fluence Photoacoustic Therapy Pulsed (PTP) Mode 1064 nm Q‐Switched ND‐YAG Laser for Treatment of Melasma: A Prospective Split‐Face Study
Authors: Lee So Yeon , Kim Hye Ran , Park Jin Seo , Kim Jin Cheol , Park Chun Wook , Kim Hye One , Chung Bo Young
Published: June 2023

Melasma is a challenging pigmentation disorder to treat, and although low‐fluence 1064 nm picosecond ND‐YAG lasers have shown potential for treating benign pigmented disorders, data on the use of this laser for melasma treatment are currently insufficient. In this prospective split‐face study, twenty‐four patients with melasma on the face were enrolled and randomly assigned to receive treatment on one side of the face either with a low‐fluence 1064 nm picosecond ND‐YAG laser or with a low‐fluence PTP mode 1064 nm Q‐switched ND‐YAG laser. Laser treatment was performed 5 times at intervals of 2 weeks, with evaluation conducted before each treatment and 2 months after the completion of 5 treatments. Clinical pictures using a standardized, digital photographic system and dermoscopy were taken on each day of the visit. The modified melasma area severity index (mMASI), melanin index (MI), dermoscopic scores of the pigmentary and vascular elements in melasma, pain during laser treatment, and patient satisfaction score were recorded. Twenty‐one participants completed the study, and from week 2 in both groups, a significant decrease in mMASI and MI were confirmed. Although no statistically significant difference was observed, the decrease in mMASI and MI were greater in the 1064 nm picosecond ND‐YAG laser group than in the 1064 nm Q‐switched ND‐YAG laser group. The 1064 nm picosecond ND‐YAG laser group showed significant improvement in the pseudoreticular network and globular pattern of dermoscopic features between week 0 and week 16, while significant improvement in the globular pattern was shown in the 1064 nm Q‐switched ND‐YAG laser group. No significant difference was observed between the two groups in terms of the patient satisfaction score and pain during laser treatments. Notably, no adverse events were observed in either group. In conclusion, our study demonstrated that a low‐fluence 1064 nm picosecond ND‐YAG laser is as effective and safe in the treatment of melasma as a low‐fluence PTP mode 1064 nm Q‐switched ND‐YAG laser.
PDCA from Theory to Effective Applications: A Case Study of Design for Reducing Human Error in Assembly Process
Authors: Nguyen Vi , Chau Chuong K. B. , Tran Thanh
Published: June 2023

This article describes an efficient and effective way to apply the PDCA (Plan-Do-Check-Act) method in the design process to meet quality and stakeholders’ expectations. Through the case study of developing a smart workstation to train workers in the assembly process with a target to reduce the defects and improve the management task, the paper explores the main barriers and success factors for the PDCA cycle implemented in complex quality improvement projects. A prototype of the new workstation design is tested and shows significant benefits not only in defect reduction and management efficiency but also in newcomers’ learning process. This research can be used as a benchmark application of PDCA in quality improvement and engineering design processes with systematic and comprehensible guidance of the cycle.
Using DEPendency of Association on the Number of Top Hits (DEPTH) as a Complementary Tool to Identify Novel Colorectal Cancer Susceptibility Loci
Authors: Lai John , Wong Chi Kuen , Schmidt Daniel F. , Kapuscinski Miroslaw K. , Alpen Karen , MacInnis Robert J. , Buchanan Daniel D. , Win Aung K. , Figueiredo Jane C. , Chan Andrew T. , Harrison Tabitha A. , Hoffmeister Michael , White Emily , Le Marchand Loic , Pai Rish K. , Peters Ulrike , Hopper John L. , Jenkins Mark A. , Makalic Enes
Published: June 2023

Background:

DEPendency of association on the number of Top Hits (DEPTH) is an approach to identify candidate susceptibility regions by considering the risk signals from overlapping groups of sequential variants across the genome.

Methods:

We applied a DEPTH analysis using a sliding window of 200 SNPs to colorectal cancer data from the Colon Cancer Family Registry (CCFR; 5,735 cases and 3,688 controls), and Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO; 8,865 cases and 10,285 controls) studies. A DEPTH score > 1 was used to identify candidate susceptibility regions common to both analyses. We compared DEPTH results against those from conventional genome-wide association study (GWAS) analyses of these two studies as well as against 132 published susceptibility regions.

Results:

Initial DEPTH analysis revealed 2,622 (CCFR) and 3,686 (GECCO) candidate susceptibility regions, of which 569 were common to both studies. Bootstrapping revealed 40 and 49 candidate susceptibility regions in the CCFR and GECCO data sets, respectively. Notably, DEPTH identified at least 82 regions that would not be detected using conventional GWAS methods, nor had they been identified by previous colorectal cancer GWASs. We found four reproducible candidate susceptibility regions (2q22.2, 2q33.1, 6p21.32, 13q14.3). The highest DEPTH scores were in the human leukocyte antigen locus at 6p21 where the strongest associated SNPs were rs762216297, rs149490268, rs114741460, and rs199707618 for the CCFR data, and rs9270761 for the GECCO data.

Conclusions:

DEPTH can identify candidate susceptibility regions for colorectal cancer not identified using conventional analyses of larger datasets.

Impact:

DEPTH has potential as a powerful complementary tool to conventional GWAS analyses for discovering susceptibility regions within the genome.
Dual Targeting of Apoptotic and Signaling Pathways in T-Lineage Acute Lymphoblastic Leukemia
Authors: Saygin Caner , Giordano Giorgia , Shimamoto Kathryn , Eisfelder Bart , Thomas-Toth Anika , Venkataraman Girish , Ananthanarayanan Vijayalakshmi , Vincent Tiffaney L. , DuVall Adam , Patel Anand A. , Chen Yi , Tan Fenlai , Anthony Stephen P. , Chen Yu , Shen Yue , Odenike Olatoyosi , Teachey David T. , Kee Barbara L. , LaBelle James , Stock Wendy
Published: June 2023

Purpose:

Relapsed T-acute lymphoblastic leukemia (T-ALL) has limited treatment options. We investigated mechanisms of resistance to BH3 mimetics in T-ALL to develop rational combination strategies. We also looked at the preclinical efficacy of NWP-0476, a novel BCL-2/BCL-xL inhibitor, as single agent and combination therapy in T-ALL.

Experimental Design:

We used BH3 profiling as a predictive tool for BH3 mimetic response in T-ALL. Using isogenic control, venetoclax-resistant (ven-R) and NWP-0476-resistant (NWP-R) cells, phosphokinase array was performed to identify differentially regulated signaling pathways.

Results:

Typical T-ALL cells had increased dependence on BCL-xL, whereas early T-precursor (ETP)-ALL cells had higher BCL-2 dependence for survival. BCL-2/BCL-xL dual inhibitors were effective against both subtypes of T-lineage ALL. A 71-protein human phosphokinase array showed increased LCK activity in ven-R cells, and increased ACK1 activity in ven-R and NWP-R cells. We hypothesized that pre-TCR and ACK1 signaling pathways are drivers of resistance to BCL-2 and BCL-xL inhibition, respectively. First, we silenced LCK gene in T-ALL cell lines, which resulted in increased sensitivity to BCL-2 inhibition. Mechanistically, LCK activated NF-κB pathway and the expression of BCL-xL. Silencing ACK1 gene resulted in increased sensitivity to both BCL-2 and BCL-xL inhibitors. ACK1 signaling upregulated AKT pathway, which inhibited the pro-apoptotic function of BAD. In a T-ALL patient-derived xenograft model, combination of NWP-0476 and dasatinib demonstrated synergy without major organ toxicity.

Conclusions:

LCK and ACK1 signaling pathways are critical regulators of BH3 mimetic resistance in T-ALL. Combination of BH3 mimetics with tyrosine kinase inhibitors might be effective against relapsed T-ALL.
A Phase I, Multicenter, Open-Label, First-in-Human Study of DS-6157a in Patients with Advanced Gastrointestinal Stromal Tumor
Authors: George Suzanne , Heinrich Michael C. , Somaiah Neeta , Oppelt Peter , McLeod Robert , Nishioka Satoshi , Kundu Madan G. , Qian Xiaozhong , Kumar Prasanna , Laadem Abderrahmane , Lau Yvonne , Tran Brittany P. , Fallon Maura , Dosunmu Ololade , Shi Julia , Naito Yoichi
Published: June 2023

Purpose:

To evaluate DS-6157a, an antibody–drug conjugate targeting G protein–coupled receptor 20 (GPR20), in gastrointestinal stromal tumors (GIST).

Patients and Methods:

In this phase I multicenter, open-label, multiple-dose study, patients with previously treated advanced GIST received intravenous DS-6157a on Day 1 of 21-day cycles, with a starting dose of 1.6 mg/kg. The primary objective evaluated the safety and tolerability of DS-6157a, while determining dose-limiting toxicity (DLT) and the MTD. Secondary objectives included plasma pharmacokinetics parameters, plasma antidrug antibodies (ADA), and efficacy.

Results:

A total of 34 patients enrolled. DS-6157a was well tolerated, with DLTs in 4 patients (11.8%) at doses of 6.4 mg/kg, 9.6 mg/kg, and 12.8 mg/kg; the MTD was determined to be 6.4 mg/kg. Treatment-emergent adverse events (TEAE) grade ≥3 occurred in 17 patients (50.0%), including decreased platelet count (23.5%), anemia (20.6%), decreased neutrophil count (14.7%), and decreased white blood cell count (11.8%). Four patients (11.8%) experienced serious adverse events related to DS-6157a. Six patients died with 5 due to disease progression and 1 due to DS-6157a-related TEAE. Tumor shrinkage was observed in 7 patients (20.6%), and 1 patient (2.9%) achieved a partial response. Plasma concentrations and exposure of intact DS-6157a, DXd, and total anti-GPR20 antibody all demonstrated a dose-dependent profile. No treatment-emergent ADAs were observed.

Conclusions:

Targeting GPR20 with DS-6157a was tolerated in patients with advanced GIST with tumor shrinkage demonstrated in KIT/PDGFRA wild-type GIST. However, the study did not proceed further due to lower efficacy outcomes than anticipated.
Nrf2 Drives Hepatocellular Carcinoma Progression through Acetyl-CoA–Mediated Metabolic and Epigenetic Regulatory Networks
Authors: Xi Caixia , Pang Junfeng , Barrett Amanda , Horuzsko Anatolij , Ande Satyanarayana , Mivechi Nahid F. , Zhu Xingguo
Published: June 2023

Correlations between the oxidative stress response and metabolic reprogramming have been observed during malignant tumor formation; however, the detailed mechanism remains elusive. The transcription factor Nrf2, a master regulator of the oxidative stress response, mediates metabolic reprogramming in multiple cancers. In a mouse model of hepatocellular carcinoma (HCC), through metabolic profiling, genome-wide gene expression, and chromatin structure analyses, we present new evidence showing that in addition to altering antioxidative stress response signaling, Nrf2 ablation impairs multiple metabolic pathways to reduce the generation of acetyl-CoA and suppress histone acetylation in tumors, but not in tumor-adjacent normal tissue. Nrf2 ablation and dysregulated histone acetylation impair transcription complex assembly on downstream target antioxidant and metabolic regulatory genes for expression regulation. Mechanistic studies indicate that the regulatory function of Nrf2 is low glucose dependent, the effect of which is demolished under energy refeeding. Together, our results implicate an unexpected effect of Nrf2 on acetyl-CoA generation, in addition to its classic antioxidative stress response regulatory activity, integrates metabolic and epigenetic programs to drive HCC progression.

Implications:

This study highlights that Nrf2 integrates metabolic and epigenetic regulatory networks to dictate tumor progression and that Nrf2 targeting is therapeutically exploitable in HCC treatment.
A Novel Type of Monocytic Leukemia Stem Cell Revealed by the Clinical Use of Venetoclax-Based Therapy
Authors: Pei Shanshan , Shelton Ian T. , Gillen Austin E. , Stevens Brett M. , Gasparetto Maura , Wang Yanan , Liu Lina , Liu Jun , Brunetti Tonya M. , Engel Krysta , Staggs Sarah , Showers William , Sheth Anagha Inguva , Amaya Maria L. , Minhajuddin Mohammad , Winters Amanda , Patel Sweta B. , Tolison Hunter , Krug Anna E. , Young Tracy N. , Schowinsky Jeffrey , McMahon Christine M. , Smith Clayton A. , Pollyea Daniel A. , Jordan Craig T.
Published: June 2023

The BCL2 inhibitor venetoclax has recently emerged as an important component of acute myeloid leukemia (AML) therapy. Notably, use of this agent has revealed a previously unrecognized form of pathogenesis characterized by monocytic disease progression. We demonstrate that this form of disease arises from a fundamentally different type of leukemia stem cell (LSC), which we designate as monocytic LSC (m-LSC), that is developmentally and clinically distinct from the more well-described primitive LSC (p-LSC). The m-LSC is distinguished by a unique immunophenotype (CD34−, CD4+, CD11b−, CD14−, CD36−), unique transcriptional state, reliance on purine metabolism, and selective sensitivity to cladribine. Critically, in some instances, m-LSC and p-LSC subtypes can co-reside in the same patient with AML and simultaneously contribute to overall tumor biology. Thus, our findings demonstrate that LSC heterogeneity has direct clinical significance and highlight the need to distinguish and target m-LSCs as a means to improve clinical outcomes with venetoclax-based regimens.

Significance:

These studies identify and characterize a new type of human acute myeloid LSC that is responsible for monocytic disease progression in patients with AML treated with venetoclax-based regimens. Our studies describe the phenotype, molecular properties, and drug sensitivities of this unique LSC subclass.

This article is featured in Selected Articles from This Issue, p. 1949
Unprovoked Extensive Deep Vein Thrombosis due to May-Thurner Syndrome in a Young Male
Authors: Almehairi Shamma Khamis , Baniambalath Zufana Nazir
Published: June 2023

It is extremely uncommon for young adults to develop unprovoked deep venous thrombosis (DVT), the majority of the cases can be attributed to inherited thrombophilia; however, some rare cases test negative for thrombophilia, in these cases the most likely cause is an anatomic or congenital abnormality of the inferior vena cava or the iliac veins such as May-Thurner syndrome (MTS). MTS, an anatomic variant of the iliac vessels, described in 1957 by Dr. May and Dr. Thurner as the atypical positioning of the right common iliac artery over the left common iliac vein causing it to get obstructed. In this study, we report a rare case of a 36-year-old male that presented with acute left lower limb swelling, Investigations confirmed the presence of an unprovoked extensive left lower extremity DVT with bilateral MTS involving both the right and left common iliac veins. Hence, MTS and other vascular anomalies or variants must be considered in the differential diagnosis of unprovoked DVT in young adults.
Pleuraerguss-Rezidive: Einschätzung und Planung sind durch Thoraxsonographie und Thorakozentese möglich
Authors: Stanzel Franz
Published: June 2023

Background: The value of pre-booked repeated thoracentesis in patients with recurrent pleural effusion is reliant on the estimation of time to next drainage. Identifying factors associated with rapid pleural fluid recurrence could be supportive. Objective: We aimed to evaluate the ability of the patient and physician to predict the time to next therapeutic thoracentesis and to identify characteristics associated with rapid pleural fluid recurrence. Method: In a prospective, observational study, patients with recurrent unilateral pleural effusion and the physician were to predict the time to next symptom-guided therapeutic thoracentesis. Primary outcome was difference between days to actual thoracentesis and days predicted by the patient and the physician. Factors associated with pleural fluid recurrence within 60-day follow-up were assessed using Cox regression analysis. Results: A total of 98 patients were included, 71% with malignant pleural effusion. Patients’ and physicians’ predictions numerically deviated by 6 days from the actual number of days to re-thoracentesis (IQR 2–12 and 2–13, respectively). On multivariate analyses, factors associated with increased hazard of pleural fluid recurrence included daily fluid production (HR 1.35 [1.16–1.59], p > 0.001) and large effusion size (HR 2.76 [1.23–6.19], p = 0.01). Septations were associated with decreased hazard (HR 0.48 [0.24–0.96], p = 0.04).
Recent Developments in Diagnostic and Prognostic Biomarkers for Colorectal Cancer: A Narrative Review
Authors: Giannopoulou Nefeli , Constantinou Constantina
Published: June 2023

Background: Colorectal cancer was reported as the second most common cause of cancer death worldwide, in the year 2020. This disease is an important public health problem considering its high incidence and mortality rates. Summary: The molecular events that lead to colorectal cancer include genetic and epigenetic abnormalities. Some of the most important molecular mechanisms involved include the APC/β-catenin pathway, the microsatellite pathway, and the CpG island hypermethylation. Evidence in the literature supports a role for the microbiota in the development of colon carcinogenesis, and specific microbes may contribute to or prevent carcinogenesis. Progress in prevention, screening, and management has improved the overall prognosis of the disease when diagnosed at an early stage; yet metastatic disease continues to have a poor long-term prognosis due to late-stage diagnosis and treatment failure. Biomarkers are a key tool for early detection and prognosis and aim to reduce morbidity and mortality associated with colorectal cancer. The main focus of this narrative review is to provide an update on the recent development of diagnostic and prognostic biomarkers in stool, blood, and tumor tissue samples. Key Messages: The review focuses on recent investigations in microRNAs, cadherins, Piwi-interacting RNAs, circulating cell-free DNA, and microbiome biomarkers which can be applied for the diagnosis and prognosis of colorectal cancer.
Intralesional Chemotherapy for Prostate Cancer: In vivo Proof of Principle
Authors: Jotatsu Yura , Shigemura Katsumi , Arbiser Jack L , Moriwaki Michika , Hirata Yuto , Maeda Koki , Yang Young-min , Fujisawa Masato
Published: June 2023

Introduction: Prostate cancer (PCA) is one of the most common cancers in the world, and current therapies are debilitating to patients. To develop a novel modality for the treatment of PCA, we evaluated the efficacy of intralesional administration of the Sirt3 activator Honokiol (HK) and the NADPH oxidase inhibitor Dibenzolium (DIB). Methods: We used a well-established transgenic adenocarcinoma mouse prostate (TRAMP-C2) model of hormone-independent PCA. MTS assay, apoptosis assay, wound healing assay, transwell invasion assay, RT-qPCR, and Western blotting were conducted in vitro, and HK and DIB were intratumorally administered to mice bearing TRAMP-C2 tumors. Tumor size and weight were observed over time. After removing tumors, H-E staining and immunohistochemistry (IHC) staining were conducted. Results: Treatment by HK or DIB showed an inhibitory effect on cell proliferation and migration in PCA cells. Poor ability to induce apoptosis in vitro, insufficient expression of caspase-3 on IHC staining, and increased necrotic areas on H-E staining indicated that necrosis plays an important role in cell death in treating groups by HK or DIB. RT-PCR, Western blotting, and IHC staining for epithelial mesenchymal transition (EMT) markers suggested that EMT was suppressed by HK and DIB individually. In addition, HK induced activation of CD3. Mouse experiments showed safe antitumor effects in vivo. Conclusions: HK and DIB suppressed PCA proliferation and migration. Further research will explore the effects of HK and DIB at the molecular level to reveal new mechanisms that can be exploited as therapeutic modalities.
Availability of Genetic Tests in Public Health Services in Brazil: Data from the Brazilian Rare Diseases Network
Authors: de Oliveira Bibiana Mello , Neiva Mariane Barros , Carvalho Isabelle , Schwartz Ida Vanessa Doederlein , Alves Domingos , Felix Temis Maria ,   Raras Network Group
Published: June 2023

Introduction: The Brazilian Policy for Comprehensive Care for People with Rare Diseases (BPCCPRD) was published in 2014, accrediting several reference centers and incorporating many genetic tests for the diagnosis of rare diseases (RDs). The Brazilian Network of Rare Diseases (RARAS) comprises more than 40 institutions that offer diagnosis and treatment for RDs in Brazil. This network includes Reference Services for Rare Diseases (RDRS), Reference Services for Newborn Screening (NSRS), and University Hospitals distributed in all Brazilian regions. Objective: The aim of the study was to map the availability and distribution of the BPCCPRD diagnostic procedures in the Brazilian Unified Health System through RARAS. Method: Data were collected through a questionnaire on the Research Electronic Data Capture platform, with 22 questions regarding the availability of procedures. Thirty-seven coordinators from RARAS participating centers received the questionnaire link for participation by email from August/2020 to March/2021. All participating institutions ethically approved this project. Results: Of the 37 institutions, 23 (62.16%) offered cytogenetic tests, 20 (54.05%) offered molecular procedures, and 22 (59.46%) offered inborn errors of metabolism diagnostic tests. The Southern blot analysis, enzyme assays on cultured tissue and urinary organic acid tests had the highest outsourcing rate. On the other hand, the procedures most frequently performed on-site were bone marrow karyotype and long-term cultured karyotype. It was observed that 10 of the 37 centers (27%) did not provide access to investigated procedures (on-site or outsourced). The North and Midwest regions stood out in terms of the unavailability of such techniques in at least 40% of the evaluated institutions. Discussion and Conclusion: This study reveals large discrepancies in the supply of diagnostic procedures in the Brazilian territory. Moreover, there is a broad collaboration between services through the outsourcing of multiple diagnostic techniques to address this issue. Finally, this work corroborates the importance of mapping services for the diagnosis and treatment of individuals with RDs to propose actions for the better supply and distribution of these procedures.
Anemia and Systemic Inflammatory Markers in Patients with Perianal Disease: Hidradenitis Suppurativa and Inflammatory Bowel Disease
Authors: Yamanaka-Takaichi Mika , Raffals Laura E. , Ehman Eric C. , Loftus Jr. Edward V. , Alavi Afsaneh
Published: June 2023

Background: Hidradenitis suppurativa (HS) and inflammatory bowel disease (IBD) have been reported to have a wide variety of overlaps in their pathogenesis, laboratory findings, and histopathology. These two diseases can form draining tunnels and are difficult to differentiate, particularly from fistulizing lesions in the perianal area. Objective: This retrospective study of HS and IBD patients with perianal lesions sought to analyze the anemia and systemic inflammation biomarkers in these disease groups. Methods: A retrospective chart review was conducted on the laboratory findings of a total of 212 patients with perianal disease – 72 with HS, 78 with IBD, and 62 with both HS and IBD – who were evaluated at Mayo Clinic between 1998 and 2021. Results: In the HS group, 45.8% of males and females were anemic, compared to 58.1% of males and 73.5% of females in the IBD group. The HS + IBD group had the highest prevalence of anemia and the lowest hemoglobin levels. The odds ratio for being anemic was 2.19 for the IBD group and 4.05 for the IBD + HS group compared to the HS group. Monocyte/lymphocyte ratio (MLR) and platelet/lymphocyte ratio (PLR) were significantly higher in the IBD group, whereas neutrophil/lymphocyte ratio (NLR) was significantly higher in the IBD + HS group. Conclusion: Our data show for the first time the prevalence of anemia in patients with HS and IBD who have perianal lesions. In addition, noninvasive biomarkers using complete blood counts such as MLR, PLR, and NLR could be useful not only in differentiating perianal HS from fistulizing perianal IBD but also in selecting treatment.
Aquatic Hemiptera inhabiting rice fields in Karaikal, Puducherry, India
Authors: M. Kandibane  , L. Gopianand
Published: June 2023

The present investigation was taken up to record the diversity and abundance of aquatic hemipterans in an irrigated rice ecosystem during kharif 2019 and rabi 2019–2020. The aquatic hemipterans were collected using a D-frame dip net at weekly intervals. This study revealed 21 species under 13 genera and nine families of Hemiptera in irrigated rice fields during kharif 2019 and rabi 2019–2020. Micronecta scutellaris (Stål, 1858) and Anisops sardeus Herrich-Schäffer, 1850 were the dominant species in both seasons. Corixidae and Notonectidae were the most abundant families. Species diversity was maximum in kharif 2019, while species richness was maximum during rabi 2019–2020. Multiple linear regression indicated that all the physicochemical characteristics and weather parameters together were responsible for significant variation in the occurrence of Corixidae (53.60%) and Notonectidae (82.40%). Based on our research, we found that rice fields serve as suitable habitats and play a crucial role in supporting diverse range of aquatic hemipterans.
New record of Lucilia cuprina (Wiedemann, 1830) (Diptera: Calliphoridae) from the Trans-Himalayan Region, cold arid desert of Kargil Ladakh, India
Authors: Hussain Mohammed , Altaf Hussain Mir  , Hidayatullah Tak  , Nassreen Fatima Kacho
Published: June 2023

Lucilia spp. commonly known as the green bottle fly, is cosmopolitan in distribution and well documented from different parts of the world. They have medical, forensic and veterinary importance. In the present study, Lucilia cuprina (Wiedemann 1830) is documented for the first time from the Trans-Himalayan region of Kargil Ladakh. It was found that this fly is fairly widespread in the study area. These flies show strong positive correlation with the temperature and weak positive correlation with the relative humidity. Therefore, fly abundance was recorded maximum in midsummer (July & August) and least in April & October; however, no fly activity was seen during winter months from November through March.
Eleocharis acutangula ssp. neotropica D.J.Rosen (Cyperaceae): a new record for southern Western Ghats, India
Authors: K. Nair Kavya , A.R. Viji
Published: June 2023

Eleocharis acutangula ssp. neotropica D.J.Rosen, is collected from Kollam district, reported here for the first time from Southern Western Ghats, India. A detailed description of plant along with relevant notes is provided here for easy identification
Putting wetland science to practice: a review
Authors: Adhya Tiasa , Dey Partha
Published: June 2023

Book review: 
Causal factors for Wetland Management and Restoration: A Concise Guide 
Author: Paul A. Keddy
eBook ISBN 978-3-031-21788-3
Published: 11 March 2023
Pages: XIII, 158 pp.
Publisher: Springer Cham.