bluuebunny/crossref_metadata_2025 huggingface dataset:
Numerical approach to evaluate the influence of water saturation on the strength of Neogene Tuff in Utsunomiya city, Japan
Authors: Ranaweera Neranjan , Togashi Yota , Osada Masahiko , Kawanoue Ryo
Published: January 2023

Evaluation of the deformation behavior due to drying is crucial in underground construction works. Especially, geological repository for High-Level Radioactive Waste (HLW) shall be carefully selected to act as a natural barrier to prevent radioactive nuclide leaks. Uniaxial Compressive Strength (UCS) is one such governing factors when designing or selecting a suitable location for such underground storage compartments or access tunnels. Since nuclide leakage through geological repositories, intact rocks UCS will vary with the drying conditions. Hence, it is vital to evaluate the behavior of UCS subject to the conditions prescribed. A variety of statistical models has been built to govern the interdependency between UCS and water content. However, there are no significant amount of research have been conducted to emphasize the UCS variation with the degree of saturation under the influence of drying condition. Numerically, Richard’s equation exact solution in Neuman boundary condition has been derived to exploit the degree of saturation with respect to time and position. Experimentally, obtain the UCS variation with the degree of saturation pertaining to the Neogene Tuff in Utsunomiya city, Japan. A best fit statistical model was generated for experimental data between UCS variation and the degree of saturation. Then, the experimental saturation degree was replaced by Richard’s equation exact solution saturation degree values. Surprisingly, produced graphs for experimental data and numerical analysis data for exact solution were perfectly overlapped. Results point out that change of UCS shows similar characteristics, which exponentially decrease, with both experimental saturation values and exact solution saturation values influenced the drying condition. Moreover, it suggests that UCS value can be predicted subject to the time and position in the sedimentary rocks under drying conditions.
US boosts semiconductor industry with $280bn CHIPS act
Authors: Gwynne Peter
Published: January 2023

The $280bn CHIPS and Science Act, signed on 9 August, aims to stimulate research and innovation in the US semiconductor industry as well as encouraging US companies to invest in onshore production.
Winds of change
Authors: McKenzie James
Published: January 2023

Ships may be the lifeblood of the global economy, but they’re dirty and polluting. James McKenzie wonders if a new generation of wind-powered vessels could be the answer.
The power of the wind
Authors: Lovins Amory
Published: January 2023

A response to the letter by Tim Palmer, who criticized wind power for being susceptible to drops in wind strength.
Horror story
Authors: Higgs Tom
Published: January 2023

A response to the article “From intern to chief of staff”, in which the physicist Oliver Grimston described his career with oil and gas company bp, for which he currently works as its chief of staff in Iraq.
Art, science and the Anthropocene
Authors: Randall Ian
Published: January 2023

Ian Randall reviews Tomorrow’s Parties: Life in the Anthropocene, edited by Jonathan Strahan.
Investments by the IOP
Authors: Spackman Michael , Roche Olivia
Published: January 2023

A response to two letters that called on the Institute of Physics (IOP) to end any investments in defence or in fossil fuels.
Medical physics in 22 tales
Authors: Freeman Tami
Published: January 2023

Tami Freeman reviews True Tales of Medical Physics: Insights into a Life-Saving Specialty edited by Jacob Van Dyk.
Accurate and efficient prediction of vibrational circular dichroism spectra of condensed-phase systems with the generalized energy-based fragmentation method
Authors: Zhao Dongbo , Liao Kang , Hong Benkun , Li Wei , Li Shuhua
Published: January 2023

The vibrational circular dichroism (VCD) spectra could determine the molecular chirality of condensed-phase systems, but their quantum chemistry calculations are costly. The fragment-based methods have not been applied to the VCD spectra of periodic systems yet. In this work, we have extended the generalized energy-based fragmentation (GEBF) approach to accurately and efficiently compute the VCD spectra of chiral molecular crystals under periodic boundary conditions (PBCs) and macromolecules in solutions. In this approach, the Hessian matrices, atomic polar/axial tensors of a target system, are evaluated as a linear combination of the corresponding quantities from a series of small electrostatically embedded subsystems. Comparisons of GEBF and conventional VCD spectra of two large molecules show that this approach can satisfactorily reproduce the conventional computational results. Then, we applied the PBC-GEBF method to calculate the VCD spectra of a chiral molecular crystal and two macromolecules in solutions. Our results show that the experimental VCD spectrum can be roughly reproduced in terms of both band shape and vibrational peaks. The GEBF-VCD and PBC-GEBF-VCD approaches are expected to be practical tools to investigate the chirality of molecular crystals and macromolecules in solutions.
Challenging Folk-Linguistics: Grammatical and Spelling Variation in Students’ Writing in Hebrew on WhatsApp and in Essays
Authors: Finkelstein Shir , Netz Hadar
Published: January 2023

With the increasing use of mobile phones among young people, there is growing public concern about possible detrimental effects of digital writing on learners’ literacy and language skills. We ask whether and to what extent nonstandard forms typical of spoken Hebrew and of digital communication are also found in the formal writing of high-school students. To this end, we compare between two corpora of Modern Hebrew: a naturalistic corpus of 7,120 WhatsApp messages (35,085 words) written by 80 students in three classroom WhatsApp groups and a corpus of 291 school essays (34,700 words) written by 291 students. The findings indicate that a rather clear distinction is maintained between adherence to traditional formal writing in school essays as opposed to a more lenient approach on WhatsApp. The findings thus provide empirical linguistic evidence challenging the predominant folk-linguistic public ideology.
Marrying Collective Wisdom: Researcher-practitioner Collaboration in Developing ELT Textbooks
Authors: Shu Dingfang , Yang Shanshan , Sato Masatoshi
Published: January 2023

The need for collaboration between researchers and practitioners to address the research-practice gap is a long-debated topic in applied linguistics. Little is known, however, about how researchers and practitioners can collaboratively develop teaching materials, as a potential venue to narrow the gap. This study explored how two groups of professionals in China worked together to develop textbook materials and achieved bi-directional knowledge flow. In addition, the textbooks were analyzed in light of how participants contributed to the co-authored product. Interviews with four researchers and three practitioners along with their written reflections revealed relatively equal and constructive collaborative relationships in which multi-directional knowledge flow, co-creation of new knowledge, and positive emotional interactions emerged. Though subtle, the collaboration was reflected on the nature of the developed textbooks. With a nuanced interpretation of the complexity of researcher-practitioner collaboration, we highlight the emotional dimension of collaboration and the need to pay attention to the person in the collaboration when examining a research-practice relationship.
Applications of transformer-based language models in bioinformatics: a survey
Authors: Zhang Shuang , Fan Rui , Liu Yuti , Chen Shuang , Liu Qiao , Zeng Wanwen
Published: January 2023

The transformer-based language models, including vanilla transformer, BERT and GPT-3, have achieved revolutionary breakthroughs in the field of natural language processing (NLP). Since there are inherent similarities between various biological sequences and natural languages, the remarkable interpretability and adaptability of these models have prompted a new wave of their application in bioinformatics research. To provide a timely and comprehensive review, we introduce key developments of transformer-based language models by describing the detailed structure of transformers and summarize their contribution to a wide range of bioinformatics research from basic sequence analysis to drug discovery. While transformer-based applications in bioinformatics are diverse and multifaceted, we identify and discuss the common challenges, including heterogeneity of training data, computational expense and model interpretability, and opportunities in the context of bioinformatics research. We hope that the broader community of NLP researchers, bioinformaticians and biologists will be brought together to foster future research and development in transformer-based language models, and inspire novel bioinformatics applications that are unattainable by traditional methods.

Supplementary information

Supplementary data are available at Bioinformatics Advances online.
UPP2: fast and accurate alignment of datasets with fragmentary sequences
Authors: Park Minhyuk , Ivanovic Stefan , Chu Gillian , Shen Chengze , Warnow Tandy
Published: January 2023

Motivation

Multiple sequence alignment (MSA) is a basic step in many bioinformatics pipelines. However, achieving highly accurate alignments on large datasets, especially those with sequence length heterogeneity, is a challenging task. Ultra-large multiple sequence alignment using Phylogeny-aware Profiles (UPP) is a method for MSA estimation that builds an ensemble of Hidden Markov Models (eHMM) to represent an estimated alignment on the full-length sequences in the input, and then adds the remaining sequences into the alignment using selected HMMs in the ensemble. Although UPP provides good accuracy, it is computationally intensive on large datasets.

Results

We present UPP2, a direct improvement on UPP. The main advance is a fast technique for selecting HMMs in the ensemble that allows us to achieve the same accuracy as UPP but with greatly reduced runtime. We show that UPP2 produces more accurate alignments compared to leading MSA methods on datasets exhibiting substantial sequence length heterogeneity and is among the most accurate otherwise.

Availability and implementation

https://github.com/gillichu/sepp.

Supplementary information

Supplementary data are available at Bioinformatics online.
Decreased water exchange rate across blood–brain barrier in hereditary cerebral small vessel disease
Authors: Li Yingying , Ying Yunqing , Yao Tingyan , Jia Xuejia , Liang Huilou , Tang Weijun , Jia Xiuqin , Song Haiqing , Shao Xingfeng , Wang Danny J J , Wang Chaodong , Cheng Xin , Yang Qi
Published: January 2023

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and heterozygous HTRA1 mutation-related cerebral small vessel disease (CSVD) are the two types of dominant hereditary CSVD. Blood–brain barrier (BBB) failure has been hypothesized in the pathophysiology of CSVD. However, it is unclear whether there is BBB damage in the two types of hereditary CSVD, especially in heterozygous HTRA1 mutation-related CSVD.

In this study, a case-control design was used with two disease groups including CADASIL (n = 24), heterozygous HTRA1 mutation-related CSVD (n = 9) and healthy controls (n = 24). All participants underwent clinical cognitive assessments and brain MRI. Diffusion-prepared pseudo-continuous arterial spin labelling was used to estimate the water exchange rate across the BBB (kw). Correlation and multiple linear regression analyses were used to examine the association between kw and disease burden and neuropsychological performance, respectively.

Compared with the healthy controls, kw in the whole brain and multiple brain regions was decreased in both CADASIL and heterozygous HTRA1 mutation-related CSVD patients (Bonferroni-corrected P < 0.007). In the CADASIL group, decreased kw in the whole brain (β = −0.634, P = 0.001), normal-appearing white matter (β = −0.599, P = 0.002) and temporal lobe (β = −0.654, P = 0.001) was significantly associated with higher CSVD score after adjusting for age and sex. Reduced kw in the whole brain was significantly associated with poorer neuropsychological performance after adjusting for age, sex and education in both CADASIL and heterozygous HTRA1 mutation-related CSVD groups (β = 0.458, P = 0.001; β = 0.884, P = 0.008).

This study showed that there was decreased water exchange rate across the BBB in both CADASIL and heterozygous HTRA1 mutation-related CSVD patients, suggesting a common pathophysiological mechanism underlying the two types of hereditary CSVD. These results highlight the potential use of kw for monitoring the course of CADASIL and heterozygous HTRA1 mutation-related CSVD, a possibility which should be tested in future research.
Bone involvement in primary cutaneous diffuse large B-cell lymphoma, leg-type
Authors: Laurent Claire , Ram-Wolff Caroline , Ingen-Housz-Oro Saskia , Beylot-Barry Marie , Barete Stephane , Saillard Clemence , Dupuy Alain , Bagot Martine , Adamski Henri
Published: January 2023

Primary cutaneous diffuse large B-cell lymphoma, leg-type (PCDLBCL-LT) is an aggressive cutaneous lymphoma. Bone involvement is rare and poorly described. We present five cases of PCDLBCL-LT with bone localization. In four cases, the bone involvement was diagnosed during the initial staging with positron emission tomography (PET) or computed tomography (CT) scan, and in the fifth case after tibial fracture during treatment with rituximab (RTX) and polychemotherapy (PCT). PCDLBCL-LT can be asymptomatic and involve bone sites distant from cutaneous lesions. None had other extracutaneous involvement. In our series, all patients received RTX-PCT as first-line chemotherapy and all had early relapses or progression. Second-line treatments had poor efficacy. Our series shows that bone involvement seems to be associated with poor prognosis in PCDLBCL-LT. Bone localization is not diagnosed with initial thoracic–abdominal–pelvic CT when asymptomatic and affecting the limbs only. If there is a suspicion of PCDLBCL-LT, patients should undergo systematic investigation with alternative imaging techniques, including PET, both at baseline and if there is any concern during follow-up.
A Deep Learning Model for Energy-Aware Task Scheduling Algorithm Based on Learning Automata for Fog Computing
Authors: Ebrahim Pourian Reza , Fartash Mehdi , Akbari Torkestani Javad
Published: January 2023

This paper presents an artificial intelligence deep learning model for an energy-aware task scheduling algorithm based on learning automata (LA) in the Fog Computing (FC) Applications. FC is a distributed computing model that serves as an intermediate layer between the cloud and Internet of Things (IoT) to improve the quality of service. The IoT is the closest model to the wireless sensor network (WSN). One of its important applications is to create a global approach to health care system infrastructure development that reflects recent advances in WSN. The most influential factor in energy consumption is task scheduling. In this paper, the issue of reducing energy consumption is investigated as an important challenge in the fog environment. Also, an algorithm is presented to solve the task scheduling problem based on LA and measure the makespan (MK) and cost parameters. Then, a new artificial neural network deep model is proposed, based on the presented LA task scheduling fog computing algorithm. The proposed neural model can predict the relation among MK, energy and cost parameters versus VM length for the first time. The proposed model results show that all of the desired parameters can be predicted with high precision.
Persistence or regression of prediabetes and coronary artery calcification among adults without diabetes
Authors: Cho Yoosun , Chang Yoosoo , Ryu Seungho , Kim Yejin , Jung Hyun-Suk , Kang Jeonggyu , Choi In Young , Kim Chan-won , Oh Hyungseok , Wild Sarah H , Byrne Christopher D
Published: January 2023

Objective

The effect of changes in glycemic status on subclinical atherosclerosis is uncertain. We assessed the association of persistence, regression, or progression of prediabetes with coronary artery calcium score (CACS) as a measure of subclinical atherosclerosis.

Design

A cross-sectional study, comprising 126 765 adults, and longitudinal sub-study, comprising 40 622 adults (with baseline and at least 1 follow-up computed tomography scan to assess changes in CACS), were undertaken.

Methods

Changes in glycemic status over 1.5 years (interquartile range, 1.0-2.0) before the first CACS assessment were categorized according to 6 groups: persistent normoglycemia (reference), normoglycemia to prediabetes, normoglycemia to diabetes, prediabetes to normoglycemia, persistent prediabetes, and prediabetes to diabetes. Logistic regression was used to calculate the odds ratios (ORs) and 95% CIs for prevalent coronary artery calcification (CAC). Mixed models with random intercepts and random slopes were used to estimate 5-year CAC progression rates.

Results

Mean (SD) age was 41.3 (7.0) years (74.7% male) (n = 126 765). Multivariable-adjusted OR for prevalent CAC was 1.13 (95% CI, 1.08-1.18) for persistent prediabetes, 1.05 (0.98-1.12) for regression to normoglycemia, and 1.46 (95% CI, 1.27-1.67) for progression from prediabetes to diabetes, compared with persistent normoglycemia. Coronary artery calcification progression increased significantly in all prediabetes groups. Multivariable-adjusted ratio of 5-year CAC progression rates was 1.19 (95% CI, 1.16-1.22) (persistent prediabetes), 1.11 (1.07-1.14) (regression to normoglycemia), and 1.63 (95% CI, 1.26-2.10) (progression from prediabetes to diabetes).

Conclusions

Unfavorable changes in glycemic status, including persistence of prediabetes or progression to diabetes from prediabetes, were associated with increased risk of CAC.
Saline suppression to distinguish the primary aldosteronism subtype: a diagnostic study
Authors: Hashimura Hikaru , Hu Jinbo , Kobayashi Hiroki , Gwini Stella May , Shen Jimmy , Chee Nicholas Y N , Doery James C G , Chong Winston , Fuller Peter J , Abe Masanori , Li Qifu , Yang Jun
Published: January 2023

Objectives

The saline suppression test (SST) serves to confirm the diagnosis of primary aldosteronism (PA), while adrenal vein sampling (AVS) is used to subtype PA as unilateral or bilateral. Criteria that can accurately identify those with bilateral PA based on SST results could reduce the need for AVS. We previously demonstrated that a combination of plasma aldosterone concentration (PAC) < 300 pmol L−1 and a reduction in aldosterone-to-renin ratio (ARR) following recumbent SST had high specificity for predicting bilateral PA in an Australian cohort of 92 patients with PA who have undergone AVS. We sought to validate our predictive criteria in larger, independent cohorts of patients with PA.

Design

An international, multi-centre cohort study.

Methods

Data from 55 patients at Monash Health, Victoria, Australia, 106 patients from the First Affiliated Hospital of Chongqing Medical University, China, and 105 patients from Nihon University Itabashi Hospital, Japan were analysed.

Results

A combination of PAC <300 pmol L−1 and a reduction in ARR following recumbent SST predicted bilateral PA with specificities of 88.2%, 97.0%, and 100.0% in Australian, Chinese, and Japanese cohorts, respectively. This criterion could allow 22%–38% of patients with PA to bypass AVS and proceed directly to medical treatment.

Conclusion

In patients undergoing the recumbent SST, a post-saline PAC <300 pmol L−1 together with a reduction in ARR can predict bilateral PA with high specificity and may allow targeted treatment to be commenced without AVS in up to a third of patients.
Detection of driver mutations in plasma cell–free nucleic acids in differentiated thyroid neoplasm
Authors: Dutta Susmita , Tarafdar Soham , Mukhopadhyay Pradip , Bhattacharyya Nitai P , Ghosh Sujoy
Published: January 2023

Importance

This proof-of-concept paper demonstrates that driver mutations can be detected in plasma in differentiated thyroid tumors, and we were able to detect mutations in upto 80% malignant thyroid nodules. Additionally, cancer subtypes could also be predicted using a 8-gene panel. In almost 90% follicular adenoma, rat sarcoma virus (RAS) mutations were detectable. There was a strong agreement between driver mutations found in plasma samples, FNAC materials, and histopathology samples. This has potential as a noninvasive, preoperative diagnostic tool (particularly of clinical importance in indeterminate nodules) and may help in detection of residual tumor after surgery. Future research is warranted to test the role of this tool to detect tumor recurrence.

Objective

Ultrasonographic (USG) evaluation and fine-needle aspiration (FNA) are cornerstone for evaluation of thyroid neoplasm. Molecular technique including detection of driver mutation from FNA cytology (FNAC) material is an established modality. In this study, we explored the feasibility of using plasma cell–free nucleic acids to identify known driver mutations in differentiated thyroid neoplasm.

Design

Patients presenting with thyroid nodules underwent USG with Thyroid Image Reporting and Data Systems scoring and FNAC (Bethesda classification). All patients in Bethesda 3, 4, 5, 6 underwent surgery and histopathological confirmation. Patients in Bethesda 2 (cosmetic concerns, compressive symptoms) underwent surgery, and rest were presumed benign on the basis of USG, FNAC features, and clinical followup.).

Setting

Endocrinology clinic.

Participants

Subjects with thyroid nodule.

Intervention(s) or Exposure(s)

None.

Main Outcome(s) and Measure(s)

Plasma sample, FNA, and histopathology material were evaluated for driver mutations (8-gene panel comprising BRAF-V600E, RET/PTC3, RET/PTC1, TERT promoter, HRAS, NRAS, KRAS, and PAX8-PPARG).

Results

A total of 223 subjects were recruited; of these 154 were benign and 69 had differentiated thyroid cancer. We were able to detect driver mutation from plasma in 55 subjects (79.71%) of all malignant patients, and 11 patients in benign category had RAS mutation (follicular adenoma). Rest of the benign nodules did not have any detectable driver mutations.

Conclusions and Relevance

Plasma might be a viable noninvasive alternative source for detection of driver mutations (8-gene panel) in subjects with differentiated thyroid tumors and may have significant clinical utility.
Disparity in pseudohyphal morphogenic switching response to the quorum sensing molecule 2-phenylethanol in commercial brewing strains ofSaccharomyces cerevisiae
Authors: Britton Scott J , Rogers Lisa J , White Jane S , Neven Hedwig , Maskell Dawn L
Published: January 2023

Saccharomyces cerevisiae can undergo filamentous growth in response to specific environmental stressors, particularly nitrogen-limitation, whereby cells undergo pseudohyphal differentiation, a process where cells transition from a singular ellipsoidal appearance to multicellular filamentous chains from the incomplete scission of the mother-daughter cells. Previously, it was demonstrated that filamentous growth in S. cerevisiae is co-regulated by multiple signaling networks, including the glucose-sensing RAS/cAMP-PKA and SNF pathways, the nutrient-sensing TOR pathway, the filamentous growth MAPK pathway, and the Rim101 pathway, and can be induced by quorum-sensing aromatic alcohols, such as 2-phenylethanol. However, the prevalent research on the yeast-pseudohyphal transition and its induction by aromatic alcohols in S. cerevisiae has been primarily limited to the strain Σ1278b. Due to the prospective influence of quorum sensing on commercial fermentation, the native variation of yeast-to-filamentous phenotypic transition and its induction by 2-phenylethanol in commercial brewing strains was investigated. Image analysis software was exploited to enumerate the magnitude of whole colony filamentation in 16 commercial strains cultured on nitrogen-limiting SLAD medium; some supplemented with exogenous 2-phenylethanol. The results demonstrate that phenotypic switching is a generalized, highly varied response occurring only in select brewing strains. Nevertheless, strains exhibiting switching behavior altered their filamentation response to exogenous concentrations of 2-phenylethanol.
Adrenal-Specific KO of the Circadian Clock Protein BMAL1 Alters Blood Pressure Rhythm and Timing of Eating Behavior
Authors: Costello Hannah M , Crislip G Ryan , Cheng Kit-Yan , Lynch I Jeanette , Juffre Alexandria , Bratanatawira Phillip , Mckee Annalisse , Thelwell Ryanne S , Mendez Victor M , Wingo Charles S , Douma Lauren G , Gumz Michelle L
Published: January 2023

Brain and muscle ARNT-like 1 (BMAL1) is a core circadian clock protein and transcription factor that regulates many physiological functions, including blood pressure (BP). Male global Bmal1 knockout (KO) mice exhibit ∼10 mmHg reduction in BP, as well as a blunting of BP rhythm. The mechanisms of how BMAL1 regulates BP remains unclear. The adrenal gland synthesizes hormones, including glucocorticoids and mineralocorticoids, that influence BP rhythm. To determine the role of adrenal BMAL1 on BP regulation, adrenal-specific Bmal1 (ASCre/+::Bmal1) KO mice were generated using aldosterone synthase Cre recombinase to KO Bmal1 in the adrenal gland zona glomerulosa. We confirmed the localization and efficacy of the KO of BMAL1 to the zona glomerulosa. Male ASCre/+::Bmal1 KO mice displayed a shortened BP and activity period/circadian cycle (typically 24 h) by ∼1 h and delayed peak of BP and activity by ∼2 and 3 h, respectively, compared with littermate Cre- control mice. This difference was only evident when KO mice were in metabolic cages, which acted as a stressor, as serum corticosterone was increased in metabolic cages compared with home cages. ASCre/+::Bmal1 KO mice also displayed altered diurnal variation in serum corticosterone. Furthermore, these mice have altered eating behaviors where they have a blunted night/day ratio of food intake, but no change in overall food consumed compared with controls. Overall, these data suggest that adrenal BMAL1 has a role in the regulation of BP rhythm and eating behaviors.
Automatic Split-Generation for the Fukaya Category
Authors: Perutz Timothy , Sheridan Nick
Published: January 2023

We prove a structural result in mirror symmetry for projective Calabi–Yau (CY) manifolds. Let $X$ be a connected symplectic CY manifold, whose Fukaya category $\mathcal {F}(X)$ is defined over some suitable Novikov field ${\mathbb {K}}$; its mirror is assumed to be some smooth projective ${\mathbb {K}}$-variety $Y$ that is “maximally degenerating”. Suppose that some split-generating subcategory of (a $\textsf {dg}$ enhancement of) $D^bCoh( Y)$ embeds into $\mathcal {F}(X)$: we call this hypothesis “core homological mirror symmetry”. We prove that the embedding extends to an equivalence of categories, $D^{b}Coh(Y) \simeq D^{\pi }( \mathcal {F}(X))$, using Abouzaid’s split-generation criterion. The results only depend on certain formal properties of the Fukaya category, which have been established in certain cases but not in complete generality. The appendix, which can be read on its own, proves a result about Hochschild cohomology for schemes: the compatibility of the global Hochschild–Kostant–Rosenberg isomorphism with Kodaira–Spencer deformation theory.
Phenotypes, genotypes and breakpoints: an assessment of β-lactam/β-lactamase inhibitor combinations against OXA-48
Authors: Asempa Tomefa E , Kois Abigail K , Gill Christian M , Nicolau David P
Published: January 2023

Background

Two of the three recently approved β-lactam agent (BL)/β-lactamase inhibitor (BLI) combinations have higher CLSI susceptibility breakpoints (ceftazidime/avibactam 8 mg/L; meropenem/vaborbactam 4 mg/L) compared with the BL alone (ceftazidime 4 mg/L; meropenem 1 mg/L). This can lead to a therapeutic grey area on susceptibility reports depending on resistance mechanism. For instance, a meropenem-resistant OXA-48 isolate (MIC 4 mg/L) may appear as meropenem/vaborbactam-susceptible (MIC 4 mg/L) despite vaborbactam’s lack of OXA-48 inhibitory activity.

Methods

OXA-48-positive (n = 51) and OXA-48-negative (KPC, n = 5; Klebsiella pneumoniae wild-type, n = 1) Enterobacterales were utilized. Susceptibility tests (broth microdilution) were conducted with ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam, as well as their respective BL partner. Antimicrobial activity of all six agents was evaluated in the murine neutropenic thigh model using clinically relevant exposures. Efficacy was assessed as the change in bacterial growth at 24 h, compared with 0 h controls.

Results

On average, the three BL/BLI agents resulted in robust bacteria killing among OXA-48-negative isolates. Among OXA-48-positive isolates, poor in vivo activity with imipenem/relebactam was concordant with its resistant phenotypic profile. Variable meropenem/vaborbactam activity was observed among isolates with a ‘susceptible’ MIC of 4 mg/L. Only 30% (7/23) of isolates at meropenem/vaborbactam MICs of 2 and 4 mg/L met the ≥1-log bacterial reduction threshold predictive of clinical efficacy in serious infections. In contrast, ceftazidime/avibactam resulted in marked bacterial density reduction across the range of MICs, and 96% (49/51) of isolates exceeded the ≥1-log bacterial reduction threshold.

Conclusions

Data demonstrate that current imipenem/relebactam and ceftazidime/avibactam CLSI breakpoints are appropriate. Data also suggest that higher meropenem/vaborbactam breakpoints relative to meropenem can translate to potentially poor clinical outcomes in patients infected with OXA-48-harbouring isolates.
Pure Mucinous Carcinoma of the Breast: Radiologic-Pathologic Correlation
Authors: Kuzmiak Cherie M , Calhoun Benjamin C
Published: January 2023

Mucinous carcinoma (MC) of the breast is a rare, specialized subtype of invasive breast carcinoma (IBC) accounting for approximately 1% to 4% of all primary breast malignancies. Mucinous carcinoma occurs predominantly in patients who are postmenopausal or elderly. It is usually detected on screening mammography, but occasionally the patient may present with a palpable mass. The most common mammographic appearance is an equal to high density, oval or round mass with circumscribed or indistinct margins; MC can mimic a benign lesion. Histologically, MC is a well-differentiated cancer characterized by pools of mucin around neoplastic cells. Depending on mucin content, the tumor is classified as pure (≥90% mucin) or mixed (>10% and <90% mucin). Pure MCs (PMCs) are of low or intermediate nuclear grade, and the vast majority are hormone receptor–positive and human epidermal growth factor-2 receptor–negative (luminal A subtype). Pure MCs may be classified as hypocellular (type A) or hypercellular (type B) and have a lower rate of axillary lymph node involvement and more favorable prognosis than IBCs, no special type. The purpose of this article is to review the clinical features, imaging appearances, associated histopathology, and management of PMC.
Probabilistic framework for reliable optimal design of gearboxes in general-purpose industrial robots considering random use conditions
Authors: Park Jin-gyun , Yoon Heonjun , Youn Byeng D
Published: January 2023

A vertically articulated robot with 6-degrees of freedom (DoF), called a general-purpose robot, can perform a myriad of different tasks within a workspace. This paper newly presents a probabilistic framework for the reliable optimal design of gearboxes used in general-purpose industrial robots, which considers random use conditions. To account for random use conditions, the start and end positions of a single motion profile are described as the random variable, which is statistically modeled as a uniform distribution based on the assumption that we have no information about the robot use pattern. Then, each sample of the random variable is converted to the corresponding motion profile by using an on-line trajectory planner. Monte Carlo simulation is implemented for the uncertainty propagation analysis, due to the heuristic feature of the on-line trajectory planner. In the design optimization formulation, the peak torque constraint and maximum bending moment constraint are described in a probabilistic manner. The system-level lifetime is calculated by combining component scale factors. The effectiveness of the proposed framework is demonstrated by examining a case study of a gearbox size problem for a 6-DoF serial industrial robot. The benefits of this study are as follows: Firstly, the proposed framework can evaluate the performance considering random use conditions. Secondly, torque reliability and bending moment reliability are newly proposed to ensure the dynamic performance of an industrial robot. Thirdly, the system-level lifetime by combining component scale factors gives more user-oriented and intuitive measure in an industrial robot design.
A One-Step Multiplex PCR Method to Rapidly Distinguish Two Strains of Diglyphus wani (Hymenoptera: Eulophidae) Against Agromyzid Leafminers
Authors: Du Su-Jie , Xu Shi-Yun , Guo Jian-Yang , Ye Fu-Yu , Wan Wei-Jie , Liu Wan-Xue
Published: January 2023

Hymenopteran parasitoids generally show a haplo-diploid sex determination system. Haploid males are produced from unfertilized eggs, whereas diploid females develop from fertilized eggs (arrhenotokous). In some cases, diploid females develop from unfertilized eggs (thelytokous). Diglyphus wani (Hymenoptera: Eulophidae) is a biological control agent for agromyzid leafminers and have arrhenotokous and thelytokous strains. However, the morphological characteristics of two strains of D. wani are so similar that it is difficult to accurately distinguish them based on morphology. Here, a rapid molecular identification method was developed based on the mitochondrial gene cytochrome c oxidase I (COI) and one-step multiplex PCR. Two primer combinations, PC1 (Ar-F1/Th-F1/WR2) and PC2 (Ar-F1/Th-F4/WR2), were designed and repeatedly screened to distinguish two strains simultaneously, of which two special forward primers Th-F1/Th-F4 were used for the thelytokous strain and one special forward primer Ar-F1 was used for the arrhenotokous strain. In addition, a common reverse primer, WR2, was used for both strains. The PC1 and PC2 PCR assays were effective in distinguishing the two strains at different developmental stages and field colonies. This method provides a reliable, highly sensitive, and cost-effective tool for the rapid identification of the two strains of D. wani.
Quality-of-life outcomes and risk prediction for patients randomized to nivolumab plus ipilimumab vs nivolumab on LungMAP-S1400I
Authors: Unger Joseph M , Qian Lu , Redman Mary W , Tavernier Susan S , Minasian Lori , Sigal Ellen V , Papadimitrakopoulou Vassiliki A , Leblanc Michael , Cleeland Charles S , Dzingle Samuel A , Summers Thomas J , Chao Herta , Madhusudhana Sheshadri , Villaruz Liza , Crawford Jeffrey , Gray Jhanelle E , Kelly Karen L , Gandara David R , Bazhenova Lyudmila , Herbst Roy S , Gettinger Scott N , Moinpour Carol M
Published: January 2023

Background

An important issue for patients with cancer treated with novel therapeutics is how they weigh the effects of treatment on survival and quality of life (QOL). We compared QOL in patients enrolled to SWOG S1400I, a substudy of the LungMAP biomarker-driven master protocol.

Methods

SWOG S1400I was a randomized phase III trial comparing nivolumab plus ipilimumab vs nivolumab for treatment of immunotherapy-naïve disease in advanced squamous cell lung cancer. The primary endpoint was the MD Anderson Symptom Inventory–Lung Cancer severity score at week 7 and week 13 with a target difference of 1.0 points, assessed using multivariable linear regression. A composite risk model for progression-free and overall survival was derived using best-subset selection.

Results

Among 158 evaluable patients, median age was 67.6 years and most were male (66.5%). The adjusted MD Anderson Symptom Inventory–Lung Cancer severity score was 0.04 points (95% confidence interval [CI] = −0.44 to 0.51 points; P = .89) at week 7 and 0.12 points (95% CI = −0.41 to 0.65; P = .66) at week 13. A composite risk model showed that patients with high levels of appetite loss and shortness of breath had a threefold increased risk of progression or death (hazard ratio [HR] = 3.06, 95% CI = 1.88 to 4.98; P < .001) and that those with high levels of both appetite loss and work limitations had a fivefold increased risk of death (HR = 5.60, 95% CI = 3.27 to 9.57; P < .001)—compared with those with neither risk category.

Conclusions

We found no evidence of a benefit of ipilimumab added to nivolumab compared with nivolumab alone for QOL in S1400I. A risk model identified patients at high risk of poor survival, demonstrating the prognostic relevance of baseline patient-reported outcomes even in those with previously treated advanced cancer.
Bilateral Tessier no. 7 cleft with an accessory maxilla and osseous choristoma: a case report
Authors: Acevedo Fernando Miguel Almaguer , Doe Ketemepi Gabriel Victor , Hernandez Barbara Yordanis , Lambert Radisnay Guzman , Lopez Duniesky Martinez , Gonzalez Mariuska Rodriguez
Published: January 2023

Tessier no. 7 clefts are characterized by macrostomia, facial muscular diastasis and maxillary and zygomatic bone abnormalities. It is caused by a lack of ectomesenchyme formation or penetration of the maxillary and mandibular processes during the fourth and fifth weeks of development. A case of bilateral transverse facial cleft with an accessory maxilla and an osseous choristoma is presented. The diagnosis of accessory maxilla was based on clinical findings due to the inaccessibility of orthopantomography and computed tomography scan. Orbicularis oris muscle reconstruction, cheiloplasty and excision of accessory maxilla were done. Histopathological examination of the bony lesion showed an osseous choristoma. There were no postoperative complications or local recurrence of the lesion excised. This case report demonstrates the importance of early diagnosis and intervention in maxillofacial congenital anomalies. Cheiloplasty restores function and gives the patient a natural appearance. The excision of accessory bone prevents further complications in the child’s growth.
A complex surgery of spinal tuberculosis with a psoas abscess accompanied by fibula autografting: an alternative treatment of Pott’s disease
Authors: Mansour Marah , Tanta Nour , Ismail Ghina , Alsuliman Tamim , Salman Issam
Published: January 2023

The most common manifestation of skeletal tuberculosis is tuberculosis spondylitis. Symptoms may progress insidiously from back pain to cause many severe complications. Early diagnosis and management of spinal tuberculosis have special importance in prevention. We report a case of a 24-year-old female who was diagnosed with tuberculous spondylitis, complicated with psoas abscess and grade 1/5 of lower limb weakness. The patient was treated with anti-tuberculous drugs and underwent surgical debridement, interbody fusion and internal fixation accompanied by fibular autografting using a posterior-only approach and supplemental posterior spinal stabilisation on an infected background. Within 14 years of follow-up, full bone graft spinal fusion has been achieved with no major complications. According to its clinical efficacy and feasibility, this procedure is suggested to be an alternative treatment for Pott’s disease.
Unexpected long-term survival of Stage IV pancreatic cancer patient with synchronic liver metastases after multimodal therapy including upfront surgery
Authors: Obed Aiman , Siyam Mahmoud , Jarrad Amr Anwar , Abdelhadi Ody , Ababneh Muaweih , Annab Hassan , Füzesi Laszlo , Bashir Abdalla , Jarrad Anwar
Published: January 2023

We report the case of a 56-year-old male with pancreatic cancer and 25 liver metastases. The patient underwent a distal pancreatectomy with 11 metastasectomies in the left liver lobe. Histological examination demonstrated a moderately differentiated ductal adenocarcinoma with pT3N0M1, Stage IVb. Three weeks later, we performed transarterial chemoembolization for the right lobe of the liver, and after 6 weeks we started systemic chemotherapy with FOLFIRINOX. After 31 months, computer tomography examination showed increases in size of the remaining lesions at segment VII/VIII of the right lobe. All liver metastases were surgically removed and a new chemotherapy was initiated. Nevertheless, after 40 months the patient developed two brain metastases. One was surgically resected and the smaller lesion was treated by gamma knife. Unfortunately, the patient died 42 months after the first presentation. Conclusively, in very selected patients with synchronic liver metastasis, multimodal treatment including repeated surgery, TACE and chemotherapy may prolong survival.
A statistical analysis of the catalogues and criticism of the 19th-century Paris Fine Art Salon: The emergence of titling in the French art world
Authors: Bowman Mike
Published: January 2023

The dominant institution in the French art world for the display of new art for most of the 19th century was the Paris Salon. Artistic reputations depended upon showing works at the Salon, and critics made their names through writing about the event. In this article, statistical analysis of the contents and structure of the catalogues of the Salon and of Salon criticism is utilized to understand how the practice of titling new paintings emerged and was adopted in the 19th-century French art world. My work shows how statistical methods can be used to investigate practical and conceptual change, and problematizes accounts of the emergence of titling given by earlier authors. There are also methodological lessons for those working in the digital humanities from the approach adopted in this article.
Comparison of virulence factors and susceptibility profiles of Malassezia furfur from pityriasis versicolor patients and bloodstream infections of preterm infants
Authors: Rhimi Wafa , Chebil Wissal , Ugochukwu Iniobong Chukwuebuka Ikenna , Babba Hamouda , Otranto Domenico , Cafarchia Claudia
Published: January 2023

In spite of the increasing medical interest in Malassezia yeasts, the virulence factors of Malassezia furfur causing bloodstream infections (BSI) were never investigated. Therefore, phospholipase (Pz), lipase (Lz), hemolysin (Hz), biofilm production, and in vitro antifungal susceptibility profiles were evaluated in M. furfur strains, isolated from both pityriasis versicolor (PV) patients (n = 18; Group 1) or from preterm infants BSI (n = 21; Group 2). All the test stains exhibited Pz activity, whereas 92.3% and 97.4% of strains exhibited Lz and Hz activities, respectively. Pz, Lz, and Hz activities were higher (i.e., lower values) within Group 1 strains (i.e., 0.48, 0.40, and 0.77) than those within Group 2 (i.e., 0.54, 0.54, and 0.81). The biofilm production was higher within Malassezia isolates from Group 2 (0.95 ± 0.3) than from Group 1 (0.72 ± 0.4). Itraconazole and posaconazole were the most active drugs against M. furfur, followed by amphotericin B and fluconazole. The minimum inhibitory concentrations (MIC) values varied according to the origin of M. furfur strains being statistically lower in M. furfur from Group 1 than from Group 2. This study suggests that M. furfur strains produce hydrolytic enzymes and biofilm when causing PV and BSI. Data show that the phospholipase activity, biofilm production, and a reduced antifungal susceptibility profile might favor M. furfur BSI, whereas lipase and hemolytic activities might display a synergic role in skin infection.
Vortex weighing and dating of planets in protoplanetary discs
Authors: Rafikov Roman R , Cimerman Nicolas P
Published: January 2023

High-resolution sub-mm observations of some protoplanetary discs reveal non-axisymmetric features, which can often be interpreted as dust concentrations in vortices that form at the edges of gaps carved out by the embedded planets. We use recent results on the time-scale for the planet-driven vortex development in low-viscosity discs to set constraints on the mass and age of a planet producing the vortex. Knowledge of the age of the central star in a vortex-bearing protoplanetary disc system allows one to set a lower limit on the planetary mass at the level of several tens of M⊕. Also, an independent upper limit on the planetary mass would constrain the planetary age, although given the current direct imaging detection limits this constraint is not yet very stringent (it is also sensitively dependent on the disc scale height). These results can be extended to account for the history of planetary mass accretion if it is known. We apply our calculations to several protoplanetary discs harbouring vortex-like features as revealed by ALMA and set limits of (30–50) M⊕ (for disc aspect ratio of 0.1) on the minimum masses of putative planets that could be responsible for these vortices. Our vortex-based method provides an independent way of constraining the properties of embedded planets, complementary to other approaches.
Characterizing line-of-sight variability of polarized dust emission with future CMB experiments
Authors: McBride Lisa , Bull Philip , Hensley Brandon S
Published: January 2023

While Galactic dust emission is often accounted for in cosmic microwave background (CMB) analyses by fitting a two-parameter modified blackbody (MBB) model in each pixel, typically a number of such clouds are found along each line of sight and within each angular pixel, resulting in a superposition of their spectra. We study the effects of this superposition on pixel-based foreground fitting strategies by modeling the spectral energy distribution (SED) in each pixel as the integral of individual MBB spectra over various physically motivated statistical distributions of dust cloud properties. We show that fitting these SEDs with the two-parameter MBB model generally results in unbiased estimates of the CMB Stokes Q and U amplitudes per pixel, unless there are significant changes in both the dust SED and polarization angle along the line of sight, in which case significant (>10σ) biases are observed in an illustrative model. We find that the best-fitting values of the dust temperature, Td, and spectral index, βd, are significantly biased from the mean/median of the corresponding statistical distributions when the distributions are broad, suggesting that MBB model fits can give an unrepresentative picture of the physical properties of dust at microwave wavelengths if not interpreted carefully. Using Fisher matrix analysis, we determine the experimental sensitivity required to recover the parameters of the Td and βd distributions by fitting a probabilistic MBB model, finding that only the parameters of broad distributions can be measured by SED fitting on a single line of sight.