bluuebunny/crossref_metadata_2025 huggingface dataset:
Covalent Organic Frameworks as a Versatile Platform for Iron‐Catalyzed sp3 C−H Activation and Cross‐Coupling via Decarboxylative Oxidation
Authors: Cifuentes Jhonny M. C. , Henrique Fábio J. F. S. , Ligiéro Carolina B. P. , Esteves Pierre M. , Buarque Camilla D.
Published: February 2024

This work demonstrates the oxidative cross‐coupling of cinnamic acids with toluene using FeCl3 immobilized on a covalent organic framework (COF) pore wall, resulting in the synthesis of 1,3‐arylpropene derivatives. This iron‐based heterogeneous catalytic system affords the desired products in moderate yields ranging from 51 % to 65 %. Investigations using COFs with varying pore sizes indicate that larger pores facilitate the reaction, suggesting a spatial requirement for this transformation within the catalyst. The correlation between pore size and reaction efficiency provides insights into developing tailored catalysts to match the spatial requirements of the transformation. This version emphasizes the novelty of the study and the synthesis of 1,3‐arylpropene derivatives. It also clarifies that the iron‐based heterogeneous catalytic system is responsible for the reaction. Additionally, it provides a more detailed explanation of the findings regarding pore size and spatial requirements.
Monocopper model of CuB site of pMMO in N4‐environment oxidizes C−H bonds
Authors: Hernández‐Toledo Hugo C. , Flores‐Alamo Marcos , Castillo Ivan
Published: February 2024

Discrepancies regarding the coordination environment, donor atoms, nuclearity, and oxidation state of the active site of particulate methane monooxygenase (pMMO), a copper‐dependent enzyme capable of activating the strong C−H bond of methane, persist despite numerous structural and spectroscopic studies. To address the proposed mono‐ (CuII) or bimetallic (2CuI) nature of the so‐called CuB site, we report the bis(benzimidazole)‐based NMe−N,N’‐(1‐Me‐2‐CH2C7H4N2)2C6H4 ligand (N4) and its copper complexes. In the solid state [Cu(N4)(ClO4)]ClO4 features tetragonal geometry defined by the chelating ligand and an axial perchlorate; geometric and EPR parameters are very close to those reported for the CuB site. Attempts to obtain a dicopper(I) analog resulted in [Cu(N4)][CuCl2], based on spectroscopic, electrochemical, and ESI‐MS data. Although these results support the assignment of CuB as a monometallic site, air exposure of [Cu(N4)][CuCl2] leads to ligand oxidation in the structurally characterized [Cu(N4=O)Cl], raising the possibility of distorted tetragonal Cu(I) centers activating O2 and oxidizing substrates, in C−H activation chemistry that may take place at CuB.
Library Synthesis of Cyclobutanol Derivatives by Hyperbaric [2+2] Cycloaddition Reactions
Authors: Janssen Mathilde A. C. H. , Rappard Rico , van Well Michiel J. , Blanco‐Ania Daniel , Rutjes Floris P. J. T.
Published: February 2024

Cyclobutanes are attracting a growing interest in medicinal chemistry because of their unique structure and potentially advantageous pharmacological properties. Specifically, 1,3‐disubstituted cyclobutanes have been explored as conformationally restricted propyl isosteres in drug development. In this study, a concise two‐diversification‐point library of 3‐amino‐3‐[(arenesulfonyl)methyl]cyclobutanols was synthesized through a hyperbaric [2+2] cycloaddition reaction between sulfonyl allenes and benzyl vinyl ether as the key step. Three different sulfonyl allenes were used for synthesizing the core structures that were further derivatized by the addition of up to seven amines. The amino groups were incorporated in a moderate to excellent diastereoselectivity through conjugate addition to the four‐membered‐ring scaffolds. Overall, this synthesis process demonstrates the potential for further chemical expansion and fragment growth in drug development.
‘‘The past is rich in glory and knowledge’’—The intersection of indigenous evaluation and culturally responsive evaluation
Authors: Cram Fiona , LaFrance Joan , Tibbetts Katherine A.
Published: February 2024

In this article, each author describes the development of what we loosely refer to as Indigenous Evaluation (IE) within our homeplace, and how IE has contributed to and benefited from connecting with the larger stream of Culturally Responsive Evaluation (CRE). Like IE, CRE frames evaluation through a lens that privileges the worldviews of those who are minoritized and marginalized, and names and challenges the societal barriers to Indigenous wellbeing. For many Indigenous peoples, these societal barriers can be traced back to the legacies of colonization, including the theft of Indigenous territories and the disconnection of Indigenous children from their peoples and their traditions. The resulting burden of intergenerational trauma shouldered by Indigenous peoples therefore requires IE and CRE to be in service of the sovereignty, vitality, and prosperity of Indigenous peoples. This is the future our ancestors wanted for us, and what we desire for generations yet to come.
Latine evaluators and evaluation: Advancing representation and collective agency
Authors: Neubauer Leah C. , Aponte‐Soto Lisa , Guerrero Andrea
Published: February 2024

This article details how connection to the late Dr. Stafford Hood, Culturally Responsive Evaluation (CRE) and Culturally Responsive Evaluation and Assessment (CREA) provided conceptual, methodological, and affirming foundations of our collective work as Latina evaluators, knowledge co‐creators, and mobilizers. The introduction of CRE & CREA with strategic sponsorship provided by Dr. Hood are key historic moments in the legitimization and advancement of Latine evaluators within and across the American Evaluation Association (AEA) and CREA. The co‐authors, who are multiethnic and multicultural Latinas, consider LatCrit theory, collective agency, and legitimacy in relation to key moments in the evolution of Latine evaluation discourse over the last decade.
Dynamic connectivity assessment for a terrestrial predator in a metropolitan region
Authors: Gelmi‐Candusso Tiziana A , Chin Andrew TM , Thompson Connor A , McLaren Ashley AD , Wheeldon Tyler J , Patterson Brent R , Fortin Marie‐Josée
Published: February 2024

Protecting wildlife movement corridors is critical for species conservation. Urban planning often aims to create corridors for animal movement through conservation initiatives. However, research on connectivity for urban wildlife is limited. Here, we assessed connectivity for coyotes (Canis latrans) dynamically across temporal scales and demographic traits, parametrized using the habitat selection of 27 global positioning system (GPS)‐collared coyotes in the city of Toronto, Canada. The habitat selection models accounted for human population density, impervious area, vegetation density, and distance to different linear features. Results indicated that (1) vegetation‐dense areas were key for connectivity in urban areas; (2) riverbanks, railways, and areas below power lines were predicted as movement corridors; and (3) commercial and industrial clusters strongly disrupted connectivity. Spatiotemporal differences in connectivity were associated with time of day and coyote social status but not with climate and biological seasonality or coyote age and sex. Residential roads were pivotal in the temporal dynamism of connectivity. The maintenance and enhancement of plant structural complexity along key infrastructure (for example, highways, waterways, and parking lots) should be considered when managing connectivity corridors in cities.
Lymph node yield: Impact on oncologic outcomes in oral cavity cancer
Authors: Khalil Carlos , Khoury Mark , Higgins Kevin , Enepekides Danny , Karam Irene , Husain Zain Ali , Bayley Andrew , Poon Ian , Truong Tra , Chan Kelvin K. W. , Smoragiewicz Martin , Fu Rui , Eskander Antoine
Published: February 2024

Background

Lymph node metastases are associated with poor prognosis in oral cavity squamous cell carcinoma (OCSCC). In other cancers, clinical guidelines on the number of lymph nodes removed during primary surgery, lymph node yield (LNY), exist. Here, we evaluated the prognostic capacity of LNY on regional failure, locoregional recurrence, and disease‐free survival (DFS) in patients with OCSCC treated by primary neck surgery.

Methods

This retrospective cohort study took place at Sunnybrook Health Sciences Centre in Toronto, Canada and involved a chart review of all adult patients with treatment‐naive OCSCC undergoing primary neck dissection. For each outcome, we first used the maximally selected rank statistics and an optimism‐corrected concordance to identify an optimal threshold of LNY. We then used a multivariable Cox proportional hazards model to assess the association between high LNY (>threshold) and each outcome.

Results

Among the 579 patients with OCSCC receiving primary neck dissection, 61.7% (n = 357) were male with a mean age of 62.9 years (standard deviation: 13.1) at cancer diagnosis. When adjusting for sociodemographic and clinical factors, LNY >15 was significantly associated with improved DFS (adjusted HR [aHR]: 0.73, 95% CI: 0.54–0.98), locoregional recurrence (aHR: 0.68, 95% CI: 0.49–0.95), and regional failure (aHR: 0.61, 95% CI: 0.39–0.93).

Conclusions

Our study findings suggested high LNY to be a strong independent predictor of various patient‐level quality of surgical care metrics. The optimal LNY we found (15) was lower than the conventionally recommended (18), which calls for further research to establish validity in practice.
Neutrophil‐to‐lymphocyte ratio associates with nutritional parameters, intratumoral immune profiles, and clinical outcomes of pembrolizumab in head and neck squamous cell carcinoma
Authors: Morimoto Hiroki , Tsujikawa Takahiro , Miyagawa‐Hayashino Aya , Kimura Alisa , Saburi Sumiyo , Murakami Nanako , Kitamoto Kayo , Mukudai Shigeyuki , Nagao Hikaru , Saya Shibata , Ogi Hiroshi , Konishi Eiichi , Itoh Kyoko , Hirano Shigeru
Published: February 2024

Background

The relationship between the tumor‐immune microenvironment and systemic inflammatory markers, including neutrophil‐to‐lymphocyte ratio (NLR), is unclear.

Methods

We examined the characteristics of systemic inflammatory markers and tumor immune microenvironments in relation to treatment outcomes in 29 consecutive patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) who received pembrolizumab, using 14‐marker multiplex immunohistochemistry and image cytometry.

Results

NLR ≥4.5 (high NLR) at pretreatment status significantly correlated with short overall survival (OS) and progression‐free survival‐2 (PFS2) and malnutrition status. High NLR in peripheral blood was significantly correlated with low lymphoid cell and high tumor‐associated macrophage counts in tissues, especially myeloid‐to‐lymphoid cell ratios, suggesting an association between circulating and intratumoral immune complexity profiles.

Conclusions

This study suggests a link between NLR in circulating blood, systemic nutritional status, and immune composition within the tumor.
Recent Advance in the Study on 5‐Formylcytosine (f5C) RNA Modification
Authors: Wang Xin , Jin Xiao‐Yang , Cheng Liang
Published: February 2024

The widespread involvement of 5‐formylcytosine f5C RNA in gene function regulation and its impact on crucial life processes like cell differentiation, embryonic development, and disease development underscores the significance of detecting this specific base modification. This detection holds great importance for basic epigenetics research and the early diagnosis and pathogenesis research of various diseases. This review aims to summarize recent research progress in f5C detection methods using selective chemical labeling, with the hope of aiding future research endeavors.
Healing of Erosive Esophagitis and Improvement of Symptoms of Gastroesophageal Reflux Disease After Esomeprazole Treatment in Children 12 to 36 Months Old
Authors: Tolia Vasundkara , Gilger Mark A. , Barker Peter N. , Illueca Marta
Published: February 2024

Objectives:

The aim of the study was to evaluate erosive esophagitis healing and symptom improvement with once‐daily esomeprazole in children ages 12 to 36 months with endoscopically or histologically proven gastroesophageal reflux disease (GERD).

Patients and Methods:

Data from children ages 12 to 36 months were included in a post‐hoc analysis of an 8‐week, multicenter, randomized, and double‐blind by dose strata study of patients ages 1 to 11 years with endoscopically or histologically confirmed GERD. Children were randomized to receive esomeprazole 5 or 10 mg once daily. Patients underwent endoscopy and, if required, mucosal biopsy at baseline. Patients who had erosive esophagitis (graded using the Los Angeles classification system) at baseline underwent a follow‐up endoscopy at final study visit to assess healing of erosive esophagitis. Investigators scored severity of GERD symptoms at baseline and every 2 weeks using the Physician Global Assessment.

Results:

Thirty‐one of 109 primary study patients ages 12 to 36 months were included in the post hoc analysis. At baseline, 15 patients (48.4%) had erosive esophagitis, underwent follow‐up endoscopy, and were healed after 8 weeks of esomeprazole treatment. Of the 19 patients with moderate‐to‐severe baseline Physician Global Assessment symptom scores, 84.2% had lower scores by the final visit. Following esomeprazole treatment, GERD symptoms were significantly improved from baseline to final visit (P ≤ 0.0018).

Conclusions:

Esomeprazole 5 or 10 mg may be used to successfully treat erosive esophagitis and symptoms of GERD in children as young as 1 year.

Moreover, although not yet validated in pediatric patients, the Los Angeles classification system was useful in grading erosive esophagitis in children ages 12 to 36 months.
Degrees of macrophage‐facilitated healing in aneurysm occlusion devices
Authors: Donehoo Del A. , Collier Claudia A. , VandenHeuvel Sabrina N. , Roy Sanjana , Solberg Spencer C. , Raghavan Shreya A.
Published: February 2024

Insufficient healing of aneurysms following treatment with vascular occlusion devices put patients at severe risk of fatal rupture. Therefore, promoting healing and not just occlusion is vital to enhance aneurysm healing. Following occlusion device implantation, healing is primarily orchestrated by macrophage immune cells, ending with fibroblasts depositing collagen to stabilize the aneurysm neck and dome, preventing rupture. Several modified occlusion devices are available currently on‐market. Previous in vivo work demonstrated that modifications of occlusion devices with a shape memory polymer foam had enhanced aneurysm healing outcomes. To better understand cellular response to occlusion devices and improve aneurysm occlusion device design variables, we developed an in vitro assay to isolate prominent interactions between devices and key healing players: macrophages and fibroblasts. We used THP‐1 monocyte derived macrophages and human dermal fibroblasts in our cell culture models. Macrophages were allowed device contact with on‐market competitor aneurysm occlusion devices for up to 96 h, to allow for any spontaneous device‐driven macrophage activation. Macrophage secreted factors were captured in the culture media, in response to device‐specific activation. Fibroblasts were then exposed to device‐conditioned macrophage media (with secreted factors alone), to determine if there were any device‐induced changes in collagen secretion. Our in vitro studies were designed to test the direct effect of devices on macrophage activation, and the indirect effect of devices on collagen secretion by fibroblasts to promote aneurysm healing and stabilization. Over 96 h, macrophages displayed significant migration toward and interaction with all tested devices. As compared to other devices, shape memory polymer foams (SMM, Shape Memory Medical) induced significant changes in gene expression indicating a shift toward an anti‐inflammatory pro‐healing M2‐like phenotype. Similarly, macrophages in contact with SMM devices secreted more vascular endothelial growth factor (VEGF) compared with other devices. Macrophage conditioned media from SMM‐contacted macrophages actively promoted fibroblast secretion of collagen, comparable to amounts observed with exogenous stimulation via VEGF supplementation. Our data indicate that SMM devices may promote good aneurysm healing outcomes, because collagen production is an essential step to ultimately stabilize an aneurysm.
Mechanotransduction and epigenetic modulations of chromatin: Role of mechanical signals in gene regulation
Authors: Mishra Jagdish , Chakraborty Subhajit , Niharika  , Roy Ankan , Manna Soumen , Baral Tirthankar , Nandi Piyasa , Patra Samir K.
Published: February 2024

Mechanical forces may be generated within a cell due to tissue stiffness, cytoskeletal reorganization, and the changes (even subtle) in the cell's physical surroundings. These changes of forces impose a mechanical tension within the intracellular protein network (both cytosolic and nuclear). Mechanical tension could be released by a series of protein–protein interactions often facilitated by membrane lipids, lectins and sugar molecules and thus generate a type of signal to drive cellular processes, including cell differentiation, polarity, growth, adhesion, movement, and survival. Recent experimental data have accentuated the molecular mechanism of this mechanical signal transduction pathway, dubbed mechanotransduction. Mechanosensitive proteins in the cell's plasma membrane discern the physical forces and channel the information to the cell interior. Cells respond to the message by altering their cytoskeletal arrangement and directly transmitting the signal to the nucleus through the connection of the cytoskeleton and nucleoskeleton before the information despatched to the nucleus by biochemical signaling pathways. Nuclear transmission of the force leads to the activation of chromatin modifiers and modulation of the epigenetic landscape, inducing chromatin reorganization and gene expression regulation; by the time chemical messengers (transcription factors) arrive into the nucleus. While significant research has been done on the role of mechanotransduction in tumor development and cancer progression/metastasis, the mechanistic basis of force‐activated carcinogenesis is still enigmatic. Here, in this review, we have discussed the various cues and molecular connections to better comprehend the cellular mechanotransduction pathway, and we also explored the detailed role of some of the multiple players (proteins and macromolecular complexes) involved in mechanotransduction. Thus, we have described an avenue: how mechanical stress directs the epigenetic modifiers to modulate the epigenome of the cells and how aberrant stress leads to the cancer phenotype.
FFLUX molecular simulations driven by atomic Gaussian process regression models
Authors: Manchev Yulian T. , Popelier Paul L. A.
Published: February 2024

Machine learning (ML) force fields are revolutionizing molecular dynamics (MD) simulations as they bypass the computational cost associated with ab initio methods but do not sacrifice accuracy in the process. In this work, the GPyTorch library is used to create Gaussian process regression (GPR) models that are interfaced with the next‐generation ML force field FFLUX. These models predict atomic properties of different molecular configurations that appear in a progressing MD simulation. An improved kernel function is utilized to correctly capture the periodicity of the input descriptors. The first FFLUX molecular simulations of ammonia, methanol, and malondialdehyde with the updated kernel are performed. Geometry optimizations with the GPR models result in highly accurate final structures with a maximum root‐mean‐squared deviation of 0.064 Å and sub‐kJ mol−1 total energy predictions. Additionally, the models are tested in 298 K MD simulations with FFLUX to benchmark for robustness. The resulting energy and force predictions throughout the simulation are in excellent agreement with ab initio data for ammonia and methanol but decrease in quality for malondialdehyde due to the increased system complexity. GPR model improvements are discussed, which will ensure the future scalability to larger systems.
Abnormal stress promotes intervertebral disc degeneration through WTAP/YTHDF2‐dependent TIMP3 m6A modification
Authors: Gao Daokuan , Zhao Quanlai , Liu Chen , Zhang Yu , Xiao Liang
Published: February 2024

Mechanical environment worsening is an important predisposing factor that accelerates intervertebral disc degeneration (IDD), but its specific regulatory mechanisms remain unclear. In this study, we reveal the molecular mechanisms of WTAP/YTHDF2‐mediated m6A modification in abnormal stress‐induced intervertebral disc (IVD) matrix degradation. WTAP expression in human nucleus pulposus cells was elevated under tension. Similarly, high WTAP expression was detected in severe degenerated human and rat nucleus pulposus tissues. Functionally, WTAP was found to increase the TIMP3 transcript methylation level under tension, resulting in YTHDF2 recognition, binding, and induction of its degradation. Reduction in TIMP3 caused increases in active matrix metalloproteinases, ultimately inducing extracellular matrix degradation in nucleus pulposus cells. Macroscopically, this promotes IDD. Additionally, in vitro and in vivo inhibition of WTAP expression or TIMP3 overexpression significantly increased stress resistance in the nucleus pulposus, thereby alleviating IDD. Our results show that abnormal stress disrupts IVD matrix stability through WTAP/YTHDF2‐dependent TIMP3 m6A modification.
Experiences of hereditary cancer care among transgender and gender diverse people: “It's gender. It's cancer risk…it's everything”
Authors: Roth Sarah , Owczarzak Jill , Baker Kellan , Davidson Hannah , Jamal Leila
Published: February 2024

Transgender and gender diverse (TGD) individuals are a significant yet underrepresented population within genetic counseling research and broader LGBTQI+ health studies. This underrepresentation perpetuates a cycle of exclusion from the production of medical knowledge, impacting the quality and equity of care received by TGD individuals. This issue is particularly poignant in cancer genetic counseling, where TGD individuals with elevated cancer risk receive risk assessment, counseling, and referral to support based on risk figures and standards of care developed for cisgender individuals. The experiences of TGD individuals navigating inherited cancer syndromes remain largely undocumented in medical literature, posing challenges to the provision of inclusive care by genetics providers. To bridge this knowledge gap, we conducted a cross‐sectional qualitative study. Nineteen semi‐structured interviews were held with gender diverse adults having hereditary cancer syndromes, family histories of such syndromes, or personal histories of chest cancer. Our study employed thematic analysis using combined inductive and deductive methods to illuminate how hereditary cancer care intersects with participants' gender identities, gender expression, and gender‐affirming care experiences. Participants reflected on care experiences that felt affirming or triggered gender dysphoria. Participants also discussed the interplay between risk‐reducing mastectomy and top surgery, exploring co‐emergent dynamics between cancer risk management and gender expression. Significantly, participants identified actionable strategies for healthcare providers to enhance support for gender diverse patients, including the mindful use of gendered language, collaborative decision‐making, and conveying allyship. These findings offer valuable insights into tailoring genetic counseling to meet the unique needs of TGD individuals, advancing the path toward inclusive and appropriate care for LGBTQI+ individuals with hereditary cancer syndromes.
What next for “counseling” in genetic counseling training: A reflection on how CBT and ACT approaches can contribute to the genetic counseling toolkit
Authors: Davies Rachel , Price Tate Rachel , Taverner Nicola V.
Published: February 2024

Counseling techniques are an important component of genetic counseling training and are focused on the person‐centered counseling philosophy. While this has a long tradition within the profession and underpins the empowerment goal, it should not limit consideration of the potential benefits of education on other psychotherapeutic approaches such as the cognitive philosophy. The goal of empowerment in genetic counseling requires patients to receive information in a way that is accessible to them and to make sense of it in relation to their own health, lifestyle, and family information. This assimilation of new information is a complex cognitive process, and yet it is one that genetic counselors do not routinely actively facilitate. Rather the counseling component of genetic counseling has traditionally focused on emotionally supporting the patient which is driven by the person‐centered philosophy that is covered in genetic counseling training. This paper argues for the potential for adopting more cognitive approaches informed by cognitive–behavioral therapy (CBT) and acceptance and commitment therapy (ACT), as these short interventions can have wide impact, including engaging patients who do not want to discuss feelings, helping people to make sense of information (not just gain knowledge), and helping people to change the relationship they have with their thoughts. This paper advocates for an introduction to CBT and ACT to be incorporated into prequalification training and for more advanced training to be available to postqualification genetic counselors.
Interaction of BANCR in the relationship between Hashimoto’s thyroiditis and papillary thyroid carcinoma expression patterns and possible molecular mechanisms
Authors: Zhang Jiabo , Yao Lingli , Guo Yu
Published: February 2024

Background

Previous studies have established a connection between Hashimoto’s thyroiditis (HT) and an increased risk of papillary thyroid carcinoma (PTC). However, the molecular mechanisms driving this association are not well understood. The long non‐coding RNA (lncRNA) BRAF‐activated non‐coding RNA (BANCR) has been implicated in various cancers, suggesting a potential role in the HT‐PTC linkage.

Methods

This study investigated the expression levels of BANCR in PTC and HT samples, compared to control tissues. We also examined the association between BANCR expression and clinicopathological features, including lymph node metastasis. Furthermore, we explored the molecular mechanisms of BANCR in PTC pathogenesis and its potential as a therapeutic target.

Results

BANCR expression was significantly lower in PTC samples than in controls, while it was moderately increased in HT samples. In PTC cases with concurrent HT, BANCR expression was markedly reduced compared to normal tissues. Our analysis revealed BANCR’s role as an oncogene in PTC, influencing various cancer‐related signaling pathways. Interestingly, no significant correlation was found between BANCR expression and lymph node metastasis.

Conclusion

Our findings underscore the involvement of BANCR in the connection between HT and PTC. The distinct expression patterns of BANCR in PTC and HT, especially in PTC with concurrent HT, provide new insights into the molecular interplay between these conditions. This study opens avenues for the development of innovative diagnostic and therapeutic strategies targeting BANCR in PTC and HT.
Lisocabtagene maraleucel for treatment of relapsed and refractory primary mediastinal large B‐cell lymphoma in an adolescent patient
Authors: Lee Dasom , Goyal Anmol , Wang William L , Ananth Snegha , Lau Eric , Binkley Michael S , Bharadwaj Sushma , Dahiya Saurabh
Published: February 2024

The safety and efficacy of CAR T‐cell therapy are unknown in pediatric and adolescent patients with relapsed or refractory primary mediastinal large B‐cell lymphoma (R/R PMBCL) which is associated with dismal prognosis. Here, we present a case report of a 16‐year‐old patient with R/R PMBCL treated with lisocabtagene maraleucel including correlative studies. Patient achieved complete response at 6 months without cytokine release syndrome and immune effector cell‐associated neurotoxicity syndrome. She only experienced mild cytopenias, requiring filgrastim once. This report highlights the safety and efficacy of lisocabtagene maraleucel in this population, warranting prospective studies to improve clinical outcomes.
Formulation of patient dose of [177Lu]Lu‐Trastuzumab using in‐house developed freeze‐dried kit: A path forward for clinical translation
Authors: Amirdhanayagam Jeyachitra , Guleria Mohini , Sharma Rohit , Kumar Naveen , Mukherjee Archana , Das Tapas
Published: February 2024

Trastuzumab is a US‐FDA‐approved humanized monoclonal antibody used for the treatment of human epidermal growth factor receptor 2 (HER2)‐positive breast cancer. The aim of the present work is to optimize a freeze‐dried formulation of DOTA‐Trastuzumab conjugate for the preparation of patient doses of [177Lu]Lu‐Trastuzumab for radioimmunotherapy of breast cancer. The formulation of [177Lu]Lu‐Trastuzumab usually takes a long time, and thus, such a process is not suitable for the routine preparation of this agent in hospital radiopharmacies. To circumvent this, a pre‐synthesized DOTA‐Trastuzumab conjugate as a freeze‐dried formulation is proposed. In the present work, DOTA‐Trastuzumab conjugate was subjected to a freeze‐drying process after the addition of optimized amounts of radioprotectant and cryoprotectant. [177Lu]Lu‐DOTA‐Trastuzumab was prepared by incubating the lyophilized powder of the kit vial with medium‐specific activity 177LuCl3. The final radiochemical purity of [177Lu]Lu‐DOTA‐Trastuzumab, prepared using freeze‐dried kit, was determined to be >95%. To ascertain the reproducibility of the procedure, six consecutive batches of the freeze‐dried formulation were prepared, radiolabeled, and evaluated by carrying out both in vitro and ex vivo studies. The consistency of the results of all the six consecutive batches confirmed the robustness and utility of the in‐house optimized freeze‐dried formulation for the preparation of patient doses of [177Lu]Lu‐Trastuzumab at hospital radiopharmacies.
Omicron BA.4/5 neutralization and cell‐mediated immune responses in relation to baseline immune status and breakthrough infection among PLWH: A follow‐up cohort study
Authors: Zhan Haoting , Xie Yuchen , Liu Yongmei , Cheng Linlin , Xu Yi , Qu Xiaojing , Li Chen , Guo Xinru , Li Haolong , Wang Yuling , Dai Erhei , Wang Lijing , Gao Huixia , Li Yongzhe
Published: February 2024

There is a paucity of data on hybrid immunity (vaccination plus breakthrough infection [BI]), especially cell‐mediated responses to Omicron among immunosuppressed patients. We aim to investigate humoral and cellular responses to Omicron BA.4/5 among people living with HIV (PLWH) with/without BIs, the most prevalent variant of concern after the reopening of China. Based on our previous study, we enrolled 77 PLWH with baseline immune status of severe acute respiratory syndrome coronavirus 2 specific antibodies after inactivated vaccination. “Correlates of protection,” including serological immunoassays, T cell phenotypes and memory B cells (MBC) were determined in PLWH without and with BI, together with 16 PLWH with reinfections. Higher inhibition rate of neutralizing antibodies (NAb) against BA.4/5 was elicited among PLWH with BI than those without. Omicron‐reactive IL4+ CD8+ T cells were significantly elevated in PLWH experienced postvaccine infection contrasting with those did not. NAb towards wild type at baseline was associated with prolonged negative conversion time for PLWH whereas intermediate MBCs serve as protecting effectors. We uncovered that hybrid immunity intensified more protection on BA.4/5 than vaccination did. Strengthened surveillance on immunological parameters and timely clinical intervention on PLWH deficient in protection would reduce the severity and mortality in the context of coexistence with new Omicron subvariants.
A mouse xenograft long‐term replication yields a SARS‐CoV‐2 Delta mutant with increased lethality
Authors: Kim Dongbum , Kim Minyoung , Kim Jinsoo , Baek Kyeongbin , Park Heedo , Park Sangkyu , Kang Bo Min , Kim Suyeon , Kim Mo‐Jong , Mostafa Mohd Najib , Maharjan Sony , Shin Ha‐Eun , Lee Myeong‐Heon , Il Kim Jin , Park Man‐Seong , Kim Yong‐Sun , Choi Eun‐Kyoung , Lee Younghee , Kwon Hyung‐Joo
Published: February 2024

We recently established a long‐term SARS‐CoV‐2 infection model using lung‐cancer xenograft mice and identified mutations that arose in the SARS‐CoV‐2 genome during long‐term propagation. Here, we applied our model to the SARS‐CoV‐2 Delta variant, which has increased transmissibility and immune escape compared with ancestral SARS‐CoV‐2. We observed limited mutations in SARS‐CoV‐2 Delta during long‐term propagation, including two predominant mutations: R682W in the spike protein and L330W in the nucleocapsid protein. We analyzed two representative isolates, Delta‐10 and Delta‐12, with both predominant mutations and some additional mutations. Delta‐10 and Delta‐12 showed lower replication capacity compared with SARS‐CoV‐2 Delta in cultured cells; however, Delta‐12 was more lethal in K18‐hACE2 mice compared with SARS‐CoV‐2 Delta and Delta‐10. Mice infected with Delta‐12 had higher viral titers, more severe histopathology in the lungs, higher chemokine expression, increased astrocyte and microglia activation, and extensive neutrophil infiltration in the brain. Brain tissue hemorrhage and mild vacuolation were also observed, suggesting that the high lethality of Delta‐12 was associated with lung and brain pathology. Our long‐term infection model can provide mutant viruses derived from SARS‐CoV‐2 Delta and knowledge about the possible contributions of emergent mutations to the properties of new variants.
Meta‐analyses of partial correlations are biased: Detection and solutions
Authors: Stanley T. D. , Doucouliagos Hristos , Havranek Tomas
Published: February 2024

We demonstrate that all meta‐analyses of partial correlations are biased, and yet hundreds of meta‐analyses of partial correlation coefficients (PCCs) are conducted each year widely across economics, business, education, psychology, and medical research. To address these biases, we offer a new weighted average, UWLS+3. UWLS+3 is the unrestricted weighted least squares weighted average that makes an adjustment to the degrees of freedom that are used to calculate partial correlations and, by doing so, renders trivial any remaining meta‐analysis bias. Our simulations also reveal that these meta‐analysis biases are small‐sample biases (n < 200), and a simple correction factor of (n − 2)/(n − 1) greatly reduces these small‐sample biases along with Fisher's z. In many applications where primary studies typically have hundreds or more observations, partial correlations can be meta‐analyzed in standard ways with only negligible bias. However, in other fields in the social and the medical sciences that are dominated by small samples, these meta‐analysis biases are easily avoidable by our proposed methods.
Analytical framework using remote sensing and water geochemistry to assess changes in landscapes with high ecological and social value
Authors: Valvasori Guilherme Pires de Campos Godoy , Souza Diego Lacerda de , Matricardi Eraldo Aparecido Trondoli , Iorio Gustavo Soares , de Rezende Carlos Eduardo , Pedlowski Marcos A.
Published: February 2024

The Brazilian Mata Atlântica coastal rainforest suffered a dramatic reduction in size due to agricultural and mining activities since the 1500s. Most relevant fragments are in mountainous areas assigned for environmental conservation, where there is increasing market pressure to open these areas for mining operations. In this study, we created a broader framework for water basin study on mountainous regions in tropical areas of high ecological importance. Remote sensing and hydrochemical analysis were used to create a more encompassing evaluation and a prognosis of environmental changes caused by mining operations. Our results showed that land use and land cover variations affect the physical and chemical behavior of rivers, and that seasonality plays a compounding role in their levels of particulate and chemical elements. Applying these combined techniques proved to be a good strategy in the evaluation of land cover change on the physical and chemical variations found in smaller watersheds.
Design of low‐pass filter with improved equalization based on lossy grounded spoof surface plasmon polaritons
Authors: Wang Chenhao , Shi Xiaomin
Published: February 2024

A new method for designing multifunctional low‐pass filter with controllable equalizing capability is presented in this letter. By constructing the novel unit cell, namely, loading surface mount resistor on the grounded spoof surface plasmon polaritons (SSPPs), the filter not only achieves filtering and equalizing functions at the same time, but also improves the equalizing response in the low‐band effectively. To illustrate the principle, the extraction method of equivalent circuit of the lossy unit cell is introduced, and the equalization and filtering properties characterized by attenuation constant and asymptotic frequency are explored. To verify the concept, a prototype operating from 0.5 to 3.4 GHz with 10 dB equalizing value is implemented, fabricated, and measured. Good agreement is achieved between simulation and measurement. The result shows that the filter is provided with a smooth equalizing curve at the low frequency of the passband compared with the ungrounded SSPPs.
Fighting terrorism: How to position rapid response teams?
Authors: van Aken Lotte , Schlicher Loe , Slikker Marco , van Houtum Geert‐Jan
Published: February 2024

In light of recent terrorist attacks, we introduce and study a Stackelberg game between a government and a terrorist. In this game, the government positions a number of heavily‐armed rapid response teams on a line segment (e.g., a long boulevard or shopping avenue) and then the terrorist attacks a location with the highest potential impact of an attack. This potential impact, which we call damage, is the product of the time it takes the closest rapid response team to react and the damage caused per time unit, which is modeled via a damage rate function. We prove that there exists a subgame perfect Nash equilibrium that balances the possible damage on all intervals of the line segment that result from positioning the rapid response teams. We discuss the implications for various types of damage rate functions including one mimicking a busy boulevard with various hotspot locations.
Developing a statistical approach of evaluating daily maximum and minimum temperature observations from third‐party automatic weather stations in Australia
Authors: Li Ming , Shao Quanxi , Dabrowski Joel Janek , Rahman Ashfaqur , Powell Andrea , Henderson Brent , Hussain Zachary , Steinle Peter
Published: February 2024

Third‐party automatic weather stations (TPAWS) provide a compelling data source for scientists and practitioners to observe and estimate more accurate fine‐scale atmospheric conditions, including daily maximum and minimum temperature (denoted as Tmax and Tmin, respectively), than the current primary weather observation network can offer. Several uncertainties and errors arise in data from TPAWS as the quality control applied to these stations may be inadequate or ad hoc. In this study, we develop a statistical approach to evaluate the quality of daily Tmax and Tmin observations collected from TPAWS in Australia. Our approach compares a target observation with multiple types of reliable reference data, including neighbouring primary weather observations from the official Bureau of Meteorology of Australia stations, Australian Gridded Climate Data, and numerical weather prediction data. Guided by the operational requirements in terms of automation, interpretability, and simplicity as well as expandability, a separate test is formed for each type of reference data and then all the individual tests are merged to generate a single result based on a Gaussian mixture model that is used to provide the final overall assessment for each TPAWS observation. The overall assessment is made in the form of a p‐value‐based confidence score that measures the difference between the target observation and trusted reference data. Our method is validated by synthetic datasets based on high‐quality observations and is also applied to daily Tmax and Tmin observations from 184 TPAWS owned by the Department of Primary Industries and Regional Development of Western Australia. The framework can be readily applied to different regions with different reliable or trusted data sources.
A comprehensive review of molecular optimization in artificial intelligence‐based drug discovery
Authors: Xia Yuhang , Wang Yongkang , Wang Zhiwei , Zhang Wen
Published: February 2024

Drug discovery is aimed to design novel molecules with specific chemical properties for the treatment of targeting diseases. Generally, molecular optimization is one important step in drug discovery, which optimizes the physical and chemical properties of a molecule. Currently, artificial intelligence techniques have shown excellent success in drug discovery, which has emerged as a new strategy to address the challenges of drug design including molecular optimization, and drastically reduce the costs and time for drug discovery. We review the latest advances of molecular optimization in artificial intelligence‐based drug discovery, including data resources, molecular properties, optimization methodologies, and assessment criteria for molecular optimization. Specifically, we classify the optimization methodologies into molecular mapping‐based, molecular distribution matching‐based, and guided search‐based methods, respectively, and discuss the principles of these methods as well as their pros and cons. Moreover, we highlight the current challenges in molecular optimization and offer a variety of perspectives, including interpretability, multidimensional optimization, and model generalization, on potential new lines of research to pursue in future. This study provides a comprehensive review of molecular optimization in artificial intelligence‐based drug discovery, which points out the challenges as well as the new prospects. This review will guide researchers who are interested in artificial intelligence molecular optimization.
A Rapid, Scalable Laser‐Scribing Process to Prepare Si/Graphene Composites for Lithium‐Ion Batteries
Authors: Katsuyama Yuto , Yang Zhiyin , Thiel Markus , Zhang Xinyue , Chang Xueying , Lin Cheng‐Wei , Huang Ailun , Wang Chenxiang , Li Yuzhang , Kaner Richard B.
Published: February 2024

Silicon has gained significant attention as a lithium‐ion battery anode material due to its high theoretical capacity compared to conventional graphite. Unfortunately, silicon anodes suffer from poor cycling performance caused by their extreme volume change during lithiation and de‐lithiation. Compositing silicon particles with 2D carbon materials, such as graphene, can help mitigate this problem. However, an unaddressed challenge remains: a simple, inexpensive synthesis of Si/graphene composites. Here, a one‐step laser‐scribing method is proposed as a straightforward, rapid (≈3 min), scalable, and less‐energy‐consuming (≈5 W for a few minutes under air) process to prepare Si/laser‐scribed graphene (LSG) composites. In this research, two types of Si particles, Si nanoparticles (SiNPs) and Si microparticles (SiMPs), are used. The rate performance is improved after laser scribing: SiNP/LSG retains 827.6 mAh g−1at 2.0 A gSi+C−1, while SiNP/GO (before laser scribing) retains only 463.8 mAh g−1. This can be attributed to the fast ion transport within the well‐exfoliated 3D graphene network formed by laser scribing. The cyclability is also improved: SiNP/LSG retains 88.3% capacity after 100 cycles at 2.0 A gSi+C−1, while SiNP/GO retains only 57.0%. The same trend is found for SiMPs: the SiMP/LSG shows better rate and cycling performance than SiMP/GO composites.
Personalized Versus Precision Nanomedicine for Treatment of Ovarian Cancer
Authors: Garbuzenko Olga B. , Sapiezynski Justin , Girda Eugenia , Rodriguez‐Rodriguez Lorna , Minko Tamara
Published: February 2024

The response to treatment is substantially varied between individual patients with ovarian cancer. However, chemotherapy treatment plans rarely pay sufficient attention to the mentioned factors. Instead, standardized treatment protocols are usually employed for most ovarian cancer patients. Variations in an individual's sensitivity to drugs significantly limit the effectiveness of treatment in some patients and lead to severe toxicities in others. In the present investigation, a nanotechnology‐based approach for personalized treatment of ovarian carcinoma (the most lethal type of gynecological cancer) constructed on the individual genetic profile of the patient's tumor is developed and validated. The expression of predefined genes and proteins is analyzed for each patient sample. Finally, a mixture of the complex nanocarrier‐based targeted delivery system containing drug(s)/siRNA(s)/targeted peptide is selected from the pre‐synthesized bank and tested in vivo on murine cancer model using cancer cells isolated from tumors of each patient. Based on the results of the present study, an innovative approach and protocol for personalized treatment of ovarian cancer are suggested and evaluated. The results of the present study clearly show the advantages and perspectives of the proposed individual treatment approach.
Microwave Doping of Sulfur and Iron in β12 Borophene
Authors: Li Zhixuan , Guan Xinwei , Pandey Gaurav , Chahal Sumit , Bandyopadhyay Arkamita , Awasthi Kamalendra , Kumar Prashant , Vinu Ajayan
Published: February 2024

Borophene, a 2D material exhibiting unique crystallographic phases like the anisotropic atomic lattices of β12 and X3 phases, has attracted considerable attention due to its intriguing Dirac nature and metallic attributes. Despite surpassing graphene in electronic mobility, borophene's potential in energy storage and catalysis remains untapped due to its inherent electrochemical and catalytic limitations. Elemental doping emerges as a promising strategy to introduce charge carriers, enabling localized electrochemical and catalytic functionalities. However, effective doping of borophene has been a complex and underexplored challenge. Here, an innovative, one‐pot microwave‐assisted doping method, tailored for the β12 phase of borophene is introduced. By subjecting dispersed β12 borophene in dimethylformamide to controlled microwave exposure with sulfur powder and FeCl3 as doping precursors, S‐ and Fe doping in borophene can be controlled. Employing advanced techniques including high‐resolution transmission electron microscopy, Raman spectroscopy, and X‐ray photoelectron spectroscopy, confirm successful sulfur and iron dopant incorporation onto β12 borophene is confirmed, achieving doping levels of up to 11 % and 13 %, respectively. Remarkably, S‐ and Fe‐doped borophene exhibit exceptional supercapacitive behavior, with specific capacitances of 202 and 120 F g−1, respectively, at a moderate current density of 0.25 A g−1.