bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Paleozoic accretionary history of the Pearya terrane: New insights from igneous and detrital zircon signatures of the Kulutingwak Formation, Ellesmere Island, Nunavut, Canada
Authors: Koch Megan M. , McClelland William C. , Gilotti Jane A. , Kośmińska Karolina , Strauss Justin V. , Faehnrich Karol , Beranek Luke P. , Pease Victoria
Published: April 2024

The juxtaposition of the composite Pearya terrane and the northern Laurentian margin at Ellesmere Island, Nunavut, Canada, has significant ramifications for the Paleozoic tectonic history of the circum-Arctic region. Published tectonic models rely upon interpretation of the subduction-related Kulutingwak Formation as an indicator of Ordovician and/or Silurian accretion (Trettin, 1998). New igneous and detrital zircon U-Pb and Lu-Hf isotopic data from 16 samples collected in the Yelverton Inlet–Kulutingwak Fiord region of northern Ellesmere Island suggest that the Kulutingwak Formation of Trettin (1998) contains structural blocks derived from both the Pearya terrane and Silurian strata associated with the ancestral Laurentian margin. Data from this study demonstrate a complex provenance history for rocks within the Petersen Bay, Kulutingwak Fiord, and Emma Fiord fault zones, with age probability peaks of ca. 470 Ma, 650 Ma, and 960–980 Ma that suggest affinity with the Pearya terrane, and age probability peaks of ca. 1800 Ma and 2700 Ma that indicate connections to the Laurentian margin. The combination of these signatures in Kulutingwak Formation rocks suggests that the Pearya terrane was proximal to the northern Laurentian margin by Late Ordovician time. Silurian and younger strike-slip displacement on the major fault zones resulted in the incorporation of blocks derived from the Pearya terrane basement and Silurian clastic rocks into the Kulutingwak Formation. Silurian displacement along these strike-slip faults, which are integral components of the Canadian Arctic transform system, is recorded by syndepositional deformation structures in the Danish River Formation and prevented the transition from soft to hard collision of the Pearya terrane. The two-stage model for the Pearya terrane—accretion followed by significant translation—provides a process for developing complex steep terrane boundaries with contentious displacement histories that are common in accretionary orogens.
Fifteen-minute consultation: Approach to a child with congenital insensitivity to pain
Authors: Anuar Muhamad Azamin , Whitehouse Emily Rose , Varma Uma , McCullagh Gary , Hughes Imelda
Published: April 2024

The hereditary sensory and autonomic neuropathies (HSANs) are a group of rare genetic disorders characterised by variable phenotypic expression affecting both sensory and autonomic dysfunction. Diagnosing these conditions can be a challenge as the presenting symptoms can be diverse and may overlap. This often leads to a delay in referral and diagnosis.

Pain is often used by clinicians as a marker for systemic diseases. The key feature of HSAN conditions is the absence of pain perception and its consequences such as unexplained injuries. When a child presents with an unexplained injury, a diagnosis of non-accidental injuries must be considered, but rarely HSAN could be a possibility.

The diagnosis of HSANs in children is both important and rare. This article aims to discuss an approach to the diagnosis and management of HSANs.
Vesicocutaneous fistula at site of closed suprapubic tube tract as the first presenting sign of giant bladder stone
Authors: Thomas Brian , Sholklapper Tamir , Nourian Alex , Ginzburg Serge
Published: April 2024

Bladder stones represent approximately 5% of all cases of urolithiasis and are typically identified and managed long before causing irreversible renal injury. We present a case of a man in his 40s with a prior history of a gunshot wound to the abdomen who presented with leakage from a previously healed suprapubic tube tract and was found to have a giant bladder stone with a resulting renal injury. He subsequently underwent a combined open cystolithotomy and vesicocutaneous fistulotomy during his hospitalisation, which helped to improve his renal function. In addition to there being few reported cases of bladder stones >10 cm, this represents the first report in the literature of an associated decompressive ‘pop-off’ mechanism through a fistulised tract.
Nivolumab-associated immune-related filamentary keratitis
Authors: Madeira Maria , Fernandes Carla , Filipe Helena
Published: April 2024

A woman in her late 50s presented to the ophthalmology clinic having bilateral eye pain and discharge for the last month. Her medical history was significant for lung adenocarcinoma, for which she was being treated with nivolumab. Filamentary keratitis was evident at the slit-lamp examination. Regardless of ophthalmic reasons, nivolumab was suspended. Prednisolone ointment was started, with a complete remission. We present a case of steroid-responsive filamentary keratitis triggered by nivolumab. We aim to highlight the importance of prompt ophthalmology referral and the use of therapies targeting ocular surface inflammation in immune checkpoint inhibition therapy.
Digestive bleeding due to jejunal diverticula: diagnosis and management
Authors: Dagnesses Fonseca Javier Oscar , Danes Grases Juan Emmanuel , Luengo Batres Paloma , Calvo Espino Pablo
Published: April 2024

A jejunal diverticular haemorrhage is the second most common complication of jejunum diverticula. It can manifest clinically as acute upper gastrointestinal bleeding and is common to imitate acute rectal bleeding. Bleeding is usually associated with or without haemodynamic stability. Its diagnosis is challenging, requiring imaging examinations. Treatment is conservative management or surgery.
How therapeutic relationships develop in group-based telehealth and their perceived impact on processes and outcomes of a complex intervention: a qualitative study
Authors: Sousa Filho Luis Fernando , Farlie Melanie K , Haines Terry P , Malliaras Peter
Published: April 2024

Background

Therapeutic relationships are a key domain in healthcare delivery. While well-understood in in-person interventions, how therapeutic relationships develop in more complex contexts is unclear. This study aimed to understand (1) how therapeutic relationships are developed during the telehealth delivery of a group-based, complex intervention and (2) the perceived impact of these relationships on intervention processes, such as intervention delivery and engagement, and patient outcomes, such as patient safety and satisfaction.

Methods

This qualitative study, nested within a randomised controlled trial, used an interpretivist approach to explore the perceptions of 25 participants (18 patients with shoulder pain and 7 clinicians) regarding developing therapeutic relationships in a group-based, complex intervention delivered via telehealth. Semi-structured interviews were conducted within 4 weeks of the telehealth intervention period and then analysed through in-depth, inductive thematic analysis.

Results

We identified six themes: (1) ‘Patients trust clinicians who demonstrate credibility, promoting the development of therapeutic relationships’; (2) ‘Simple features and approaches shape the therapeutic relationship’, including small talk, time spent together and social observation; (3) ‘A sense of belonging and support fosters connections’, facilitated by clinicians providing individualised attention within the group; (4) ‘Developing therapeutic relationships can impact the delivery of core intervention components’, reflecting challenges clinicians faced; (5) ‘Therapeutic relationships can facilitate intervention engagement’, through enhanced patient understanding and confidence and (6) ‘Therapeutic relationships can contribute to patient safety and satisfaction’, with patients feeling more comfortable reporting intervention-related issues.

Conclusions

Therapeutic relationships were developed during group-based telehealth sessions through a set of factors that may require additional skills and effort compared with in-person interactions. While these relationships have a perceived positive impact on intervention engagement and patient outcomes, clinicians need to find a balance between building relationships and delivering the telehealth intervention with fidelity.

Trial registration number

ACTRN12621001650886.
What it is like to be manic: a response to Director
Authors: Kane Nuala B
Published: April 2024

In a recent article, Director makes the case that many individuals with bipolar disorder have the capacity to consent to many decisions while acutely manic, even when those decisions are out of character and cause harm. Referring to recent qualitative evidence, I argue that Director overlooks a key mechanism of manic incapacity, an inflexible experience of the future that impairs one’s ability to value. Without attention to the illness-specific experience of decision-making, capacity assessments risk false negatives in people with mania.
Incidence, prevalence and mortality of idiopathic pulmonary fibrosis in England from 2008 to 2018: a cohort study
Authors: Gupta Rikisha , Morgan Ann Dorothy , George Peter M , Quint Jennifer K
Published: April 2024

Background

Owing to discrepancies in methodologies and how idiopathic pulmonary fibrosis (IPF) is diagnosed it is challenging to establish a consistent understanding of the disease burden In the UK, over 10 years ago, the incidence and prevalence of IPF were reported as 2.8–8.7 per 100 000 person-years (from 2000 to 2012) and 39 per 100 000 persons (in 2012), respectively. Here, we estimated the incidence and prevalence of IPF in England from 2008 to 2018 and investigated IPF mortality.

Methods

Using Clinical Practice Research Datalink Aurum and Hospital Episode Statistics (HES) linked datasets, we estimated incidence and prevalence using four validated diagnostic-code-based algorithms. Using the registered number of deaths (from Office of National Statistics) with the underlying cause being recorded as IPF, we estimated IPF mortality for the same period.

Results

Using Aurum-based definitions, incidence increased over time by 100% for Aurum narrow (3–6.1 per 100 000 person-years) and by 25% for Aurum broad (22.4–28.6 per 100 000 person-years). However, using HES-based definitions showed a decrease in incidence over the same period and lay between the two extremes derived for Aurum-based definition. IPF mortality in 2018 was 7.9 per 100 000 person-years and increased by 53% between 2008 and 2018.

Interpretation

When using best-case definitions, incidence rose throughout the study period. Scaling this to England’s population (2018), our best estimate would be in the range of 8000–9000 new cases per year which is higher than previously reported estimates (5000–6000). This increased burden in the new cases of IPF each year impacts future health service planning and resource allocation.
Centrifuge modeling of end-bearing slender energy pile performance under temperature cycles
Authors: Chen Long , Hu Yifan , Ye Zi , Zhou Yang , Kong Gangqiang , Chen Yonghui
Published: April 2024

Slender energy pile shows a buckling deformation behavior under the coupling effect of temperature cycles and external loads, significantly affecting the long-term serviceability and even leading to the buckling failure. To investigate the thermo-mechanical performance of end-bearing slender energy piles under the long-term effect of temperature cycles, a centrifuge modeling experiment was conducted in this work, in which the temperature distribution, displacement, axial force, and bending moment of the energy pile during the long-term temperature cycle were measured. The results unveiled that the axial force of the end-bearing slender pile increases as temperature rises, potentially leading to a displacement neutral point in the lower part of the pile. Meanwhile, there was an embedding effect in the lower part of the slender pile, with a preliminary calculated embedment depth of 36.2 m. Temperature fluctuations can soften the soil at the pile end over time, diminishing the embedding effect on slender piles, and causing a reverse bending point to emerge at a depth of 45.5 m. The appearance of bending moments in the pile signaled the horizontal displacement encountered in the pile service life, warning the bearing capacity loss problem from changes in pile deflection.
Trisections induced by the Gluck surgery along certain spun knots
Authors: Isoshima Tsukasa , Ogawa Masaki
Published: April 2024

Gay and Meier asked whether or not a trisection diagram constructed by the Gluck twist on a spun or a twist spun 2-knot obtained from some method is standard. In this paper, we depict the trisection diagrams explicitly when the 2-knot is the spun [Formula: see text]-torus knot, where [Formula: see text], and show that the trisection diagram is standard when [Formula: see text]. Moreover, we introduce a notion of homologically standard for trisection diagrams and show that the trisection diagram is homologically standard for all [Formula: see text].
STABILITY AND BIFURCATION OF A PREDATOR–PREY SYSTEM WITH MULTIPLE ANTI-PREDATOR BEHAVIORS
Authors: XIA YUE , HUANG XINHAO , CHEN FENGDE , CHEN LIJUAN
Published: April 2024

In this paper, a predator–prey system with multiple anti-predator behaviors is developed and studied, where not only the prey may spread between patches but also the fear effect and counter-attack behavior of the prey are taken into account. First, the stability and existence of coexistence equilibria are presented. The unique positive equilibrium may be a saddle-node or a cusp of codimension 2. Then, various transversality conditions of bifurcations such as saddle-node bifurcation, transcritical bifurcation, Hopf bifurcation and Bogdanov–Takens bifurcation are obtained. Moreover, compared with a single strategy, the multiple anti-predator strategies are more beneficial to the persistence and the population density of prey.
VARIATIONAL PRINCIPLE FOR A FRACTAL LUBRICATION PROBLEM
Authors: ZUO YU-TING
Published: April 2024

Micro/nanoscale lubrication must take into account the fractal profile of the shaft and bearing surfaces. A new fractal rheological model is proposed to describe the properties of the non-Newtonian fluid, and a fractal variational principle is established by the semi-inverse method, and finally the Lagrange multipliers can be found in the obtained variational formulation. This work provides a new fractal approach to nano/micro lubrication.
Abelian groups whose endomorphism rings are V-rings
Authors: Amini Afshin , Amini Babak , Momtahan Ehsan
Published: April 2024

We study Abelian groups whose endomorphism rings are V-rings. Let [Formula: see text] be a non-reduced Abelian group, We prove that [Formula: see text] is a V-ring on either side if and only if [Formula: see text] where [Formula: see text] is a tame elementary Abelian group. We observe that a reduced group whose endomorphism is a V-ring, is an sp-group. Recognizing that [Formula: see text] is also an sp-group of [Formula: see text], we show that [Formula: see text] is a V-ring if and only if [Formula: see text] is a V-ring.
Symbols of mixed unitary quantum channels generated by finite unitary groups
Authors: Amosov Grigori G. , Cheremukhin Danil D.
Published: April 2024

We study the symbols of linear operators generated by a finite unitary group. Under some assumptions, it is shown that the operator can be restored from its symbol. We also introduce symbols of mixed unitary quantum channels generated by finite unitary groups. An example illustrating the technique is given.
Extreme quantum states and processes, and extreme points of general spectrahedra in finite dimensional algebras
Authors: Chiribella Giulio
Published: April 2024

Convex sets of quantum states and processes play a central role in quantum theory and quantum information. Many important examples of convex sets in quantum theory are spectrahedra, that is, sets of positive operators satisfying affine constraints. These examples include sets of quantum states with given expectation values of a set of observables, sets of multipartite quantum states with given marginals, sets of quantum measurements, channels and multitime quantum processes, as well as sets of higher-order quantum maps and quantum causal structures. This contribution provides a characterization of the extreme points of general spectrahedra, and bounds on the ranks of the corresponding operators. The general results are applied to several special cases, and then used to retrieve classic results such as Choi’s characterization of the extreme quantum channels, Parthasarathy’s characterization of the extreme quantum states with given marginals and the quantum version of Birkhoff’s theorem for qubit unital channels. Finally, we propose a notion of positive operator valued measures (POVMs) with general affine constraints for their normalization, and we characterize the extremal POVMs.
Proof of the orthogonal measurement conjecture for qubit states
Authors: Keil Andreas
Published: April 2024

The accessible information of general signal states is obtained by performing a generalized measurement. In the case that the signal alphabet consists of two states of a qubit system, it is proved that a von Neumann (orthogonal) measurement is sufficient to reach the accessible information.
Continuous observation of quantum systems
Authors: Maassen Hans
Published: April 2024

In a series of papers in the 1980s Alexander Holevo proved a classification theorem for continuous quantum measurement processes, or, as they would today be called, stationary quantum trajectories in continuous time. His main tools were functional analytic in character: starting from a Bochner-type inequality he employed dilation techniques for positive definite kernels. Here, we give an alternative, more probabilistic proof: we use weak convergence of measures and employ Lévy’s Continuity Theorem. We clarify the boundedness conditions in Holevo’s theorem, and supply a simple example from quantum optics.
Quantum soft-covering lemma with applications to rate-distortion coding, resolvability and identification via quantum channels
Authors: Atif Touheed Anwar , Pradhan S. Sandeep , Winter Andreas
Published: April 2024

We propose a quantum soft-covering problem for a given general quantum channel and one of its output states, which consists in finding the minimum rank of an input state needed to approximate the given channel output. We then prove a one-shot quantum covering lemma in terms of smooth min-entropies by leveraging decoupling techniques from quantum Shannon theory. This covering result is shown to be equivalent to a coding theorem for rate distortion under a posterior (reverse) channel distortion criterion by two of the present authors. Both one-shot results directly yield corollaries about the i.i.d. asymptotics, in terms of the coherent information of the channel. The power of our quantum covering lemma is demonstrated by two additional applications: first, we formulate a quantum channel resolvability problem, and provide one-shot as well as asymptotic upper and lower bounds. Second, we provide new upper bounds on the unrestricted and simultaneous identification capacities of quantum channels, in particular separating for the first time the simultaneous identification capacity from the unrestricted one, proving a long-standing conjecture of the last author.
Anadyr Basin Composite Tectono-Sedimentary Element, Chukotka Peninsula, NE Asia
Authors: Ershova V. B. , Antipov M. P. , Agapitov D. D. , Bordovskaya T. O. , Prokopiev A. V. , Shimanskiy S. V. , Akinin V.
Published: April 2024

The Anadyr Basin reflects the tectonic history of the Chukotka and Kamchatka peninsulas in the late Mesozoic and Cenozoic. It is located at the junction of the Novosibirsk–Chukotka, West Koryak and Koryak–Kamchatka fold and thrust belts (FTBs) along the NE margin of Eurasia. The basin includes a latest Cretaceous–Cenozoic succession that is divided by several unconformities caused by tectonic events within the surrounding thrust belts, resulting in several episodes of basin inversion, uplift and erosion. Accordingly, and in the framework of this memoir, the basin is described as a composite tectono-sedimentary element (CTSE).

Four gas and oil discoveries are known from the onshore part of the basin. The hydrocarbon prospectivity of the area is determined by the presence of latest Cretaceous–Eocene source rocks and Miocene reservoirs.

The purpose of this chapter is to provide an overview of geological and geophysical studies, as well as exploration work for oil and gas undertaken during the late Soviet period and in more recent times in the Anadyr Basin.
Kola-Kanin Monocline Composite Tectono-Sedimentary Element, Barents Sea
Authors: Drachev Sergey S. , Shkarubo Sergey I.
Published: April 2024

The Kola-Kanin Monocline Composite Tectono-Sedimentary Element (KKM CTSE) is located in the Eastern Barents Sea offshore the Kola Peninsula. Tectonically, it represents the SW rim of the East Barents Basin, one of the largest sedimentary depocentres in the Arctic. It is also an apparent SE continuation of the Finnmark Platform in the Norwegian Barents Sea; however, there are some differences between them in tectonic history and stratigraphy. The KKM CTSE is inferred to include Lower Paleozoic sedimentary rocks. These are not present in the Finnmark Platform due to the Caledonian Orogeny. The younger section includes Devonian–Lower Permian siliciclastic and carbonate rocks, and Permian–Triassic, Jurassic and Lower Cretaceous siliciclastic strata. The entire sedimentary section is up to 10 km thick and is divided into three main successions, or tectono-sedimentary elements (TSEs): (i) synrift uppermost Cambrian–Lower Ordovician; (ii) Middle Ordovician–Lower Triassic passive margin; and (iii) Middle Triassic–Lower Cretaceous (Albian) intracontinental basin. The KKM CTSE represents a potential region for the hydrocarbon exploration but numerous prospects identified there have not been drilled due to significant exploration risks caused by the monoclinal dip and the erosional truncation of the most of the KKM CTSE section.
A Review on the emerging technology of TinyML
Authors: Tsoukas Vasileios , Gkogkidis Anargyros , Boumpa Eleni , Kakarountas Athanasios
Published: April 2024

Tiny Machine Learning (TinyML) is an emerging technology proposed by the scientific community for developing autonomous and secure devices that can gather, process, and provide results without transferring data to external entities. The technology aims to democratize AI by making it available to more sectors and contribute to the digital revolution of intelligent devices. In this work, a classification of the most common optimization techniques for Neural Network compression is conducted. Additionally, a review of the development boards and TinyML software is presented. Furthermore, the work provides educational resources, a classification of the technology applications, and future directions and concludes with the challenges and considerations.
Case 324: CHANTER Syndrome
Authors: Suthar Pokhraj Prakashchandra , Hughes Kathryn , Mafraji Mustafa , Akyuz Melih , Jhaveri Miral , Dua Sumeet G.
Published: April 2024

History

A 69-year-old right-handed man with a history of substance use disorder, hypertension, and diabetes presented to the emergency department in an unresponsive state. Upon examination, apart from tachycardia (heart rate, 108 beats per minute), vital signs were within normal ranges (blood pressure, 134/102 mm Hg; temperature, 97.9 ºF (36.6 ºC); respiratory rate, 16 per minute; oxygen saturation, 96%). The patient had a Glasgow coma scale score of 8. Otherwise, the physical examination revealed no abnormalities. Prior psychiatric and surgical histories were unremarkable. There was no history of recent travel, camping, hiking, or vaccination. No family history could be obtained. Laboratory work-up revealed an elevated creatine kinase level (49 006 U/L [818.4 μkat/L]; normal reference range, 10–205 U/L [0.17–3.42 μkat/L]). An electrocardiogram showed sinus tachycardia without evidence of cardiac ischemia. An echocardiogram was unremarkable. Alanine aminotransferase (126 U/L [2.10 μkat/L]; normal reference range, 0–40 U/L [0–0.67 μkat/L]) and aspartate aminotransferase (488 U/L [8.15 μkat/L]; normal reference range, 3–44 U/L [0.05–0.74 μkat/L]) levels were elevated. Polymerase chain reaction results were negative for HIV-1, HIV-2, syphilis treponemal, and COVID-19 antibodies. The remaining routine laboratory work-up findings were within normal limits. Urine drug screening was positive for cocaine, marijuana, fentanyl, and benzodiazepines. Naloxone was administered, but the patient remained unresponsive. Intubation was performed for airway protection. Noncontrast and contrast-enhanced CT of the head and CT angiography were performed in the emergency department to rule out an acute intracranial abnormality. Multisequence MRI of the brain with administration of intravenous contrast material was ordered for further assessment. CT of the abdomen and pelvis was unremarkable (images not shown).
Design Change and Operational Consideration of the HVAC System during Nuclear Power Plant Decommissioning
Authors: Jeon Ho-Jin , Kim Chang-Lak
Published: April 2024

The heating, ventilation, and air conditioning (HVAC) system plays a crucial role in ensuring the safety of workers and preventing the release of gaseous radioactive materials into the environment during the decommissioning of a nuclear power plant (NPP). To establish an HVAC operation strategy, decommissioning phases were divided into four stages, and the HVAC systems were reclassified. In addition, assumptions have been made regarding design modifications and maintenance for the reactor containment building (RCB) HVAC, fuel handling building (FHB) HVAC, and main control room (MCR) HVAC. Based on these, for RCB HVAC operation, natural ventilation and RCB purge operation during the transition period are proposed. In the decommissioning stage, recirculation operation, entire ventilation operation consisting of continuous operation and purge operation, and finally partial ventilation operation to purify local space were proposed. Moreover, during the transition period, the FHB HVAC was proposed to operate as normal NPP, and the MCR HVAC was suggested to operate with safety‐related equipment removed.
Impact of Patient Body Posture on RF-Induced Energy Absorption by Orthopedic Plates
Authors: Yang Xiaolin , Zheng Jianfeng , Kainz Wolfgang , Chen Xuemin , Chen Ji
Published: April 2024

This study investigates variations in radiofrequency- (RF-) induced energy absorption by orthopedic plates within the human body during 1.5T and 3T magnetic resonance imaging (MRI) scans, considering diverse postures. Using the poseable Duke model, we developed typical postures (O-posture, X-posture, Y-posture, and Z-posture) and placed anatomically correct representations of various orthopedic plates within these postures. Numerical simulations were conducted to evaluate electromagnetic fields and RF-induced energy absorption in these postures near orthopedic plates during MRI scans. Comparing RF-induced energy absorption (peak spatial averaged SAR over 1 g, pSAR1g) in postured models to the original posture reveals substantial variations. The pSAR1g differences for X-posture, Y-posture, and Z-posture reach 48%, 134%, and 32% at 1.5T, and 36%, 83%, and 101% at 3T, respectively. Changing posture can lead to higher or lower pSAR1g. These findings underscore the impact of patient posture on RF-induced energy absorption in orthopedic plates on the ulna bone. The study recommends considering representative body postures in future evaluations for MR conditional labeling of passive implants. Until then, maintaining a neutral posture during MR scans is advised to mitigate unforeseen RF-induced heating risks.
Enablers of Mental Illness Stigma: A Scoping Review of Individual Perceptions
Authors: Gyamfi Sebastian , Forchuk Cheryl , Booth Richard , Luginaah Isaac
Published: April 2024

Introduction. Stigma is noted to be one of the greatest barriers to the recovery of persons with mental health problems. Stigma has been acknowledged as both an individual and a social orchestration that has an overpowering impact on the social standing of marginalized persons in a society. This study examined the extant literature to ascertain if any evidence(s) suggested a relationship between perceived public attitudes, religious and cultural beliefs, and structural violence in perpetuating stigma against persons with mental illness. Method. We applied a five‐step scoping review framework by Arksey and O’Malley to examine evidence in the literature that suggests relationships between perceptions, religious and cultural beliefs, and structural violence in perpetuating stigma. The researchers systematically conducted a literature search from six databases, including CINAHL, Ovid MEDLINE(R), ProQuest Dissertations & Theses Global, Sociology Collection, PsycINFO, and Sociological Abstracts, using search terms that included stigma, mental illness, perception, religious and cultural beliefs, and structural violence. Results. An initial search in six databases yielded 1223 articles. Checking in the Google Search engine yielded 30 more articles. After removing 25 duplicates, 1198 articles remained for title and abstract screening. After a full‐text review, 1143 articles were removed. Overall, 30 articles were selected for data extraction. Thematic analysis of the extracted data resulted in three main themes. These include perceptions about mental illness, perceptions about stigma and discrimination, and forms of stigma perception. Conclusion. This study revealed that individual perceptions of public attitudes contributed to their construction of stigma. It is incumbent on everyone to play their part in mitigating all the negative outcomes that stigma brings, especially to persons with mental illness.
Toripalimab Plus Bevacizumab as First-line Treatment for Advanced Hepatocellular Carcinoma: A Prospective, Multicenter, Single-Arm, Phase II Trial
Authors: Chen Yajin , Du Chengyou , Shen Shunli , Zhang Wu , Shan Yunfeng , Lyu Ang , Wu Jianhui , Shang Changzhen , Luo Xuan , Wei Jinxing , Xiao Heng , Qiu Jianguo , Hua Yunpeng , Wang Shutong , Wang Ting , Dai Shengjie , Zhang Shuhao , Xie Bingying , Wu Yinghao , Hao Chunyi
Published: April 2024

Purpose:

This phase II, multicenter, prospective, single-arm study aimed to evaluate the efficacy and safety of toripalimab plus bevacizumab for treating advanced hepatocellular carcinoma (HCC).

Patients and Methods:

Treatment-naïve patients with advanced HCC received toripalimab 240 mg plus bevacizumab 15 mg/kg every 3 weeks. The primary endpoints included safety and tolerability and objective response rate (ORR) assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Results:

Fifty-four patients were enrolled between April 17, 2020, and December 11, 2020. As assessed by the investigator according to RECIST v1.1, the ORR was 31.5% [95% confidence interval (CI), 19.5–45.6] and the lower bound of the 95% CI was above the prespecified boundary of 10%. The independent review committee (IRC) assessed ORR according to the modified RECIST (mRECIST), which was 46.3% (95% CI, 32.6–60.4). The median progression-free survival was 8.5 (95% CI, 5.5–11.0) and 9.8 months (95% CI, 5.6 to not evaluable) as assessed by the investigator according to RECIST v1.1 and IRC according to mRECIST criteria, respectively. The median overall survival (OS) was not reached, and the 12- and 24-month OS rates were 77.3% and 63.5%, respectively. Grade 3 or higher treatment-emergent adverse events (TEAEs) occurred in 27 patients (50.0%). The most common TEAEs were proteinuria (59.3%), hypertension (38.9%), increased aspartate aminotransferase (33.3%), increased amylase (29.6%), decreased platelet count (27.8%), and increased bilirubin levels (27.8%).

Conclusions:

Toripalimab plus bevacizumab showed a favorable efficacy and safety profile, supporting further studies on this combination regimen as a first-line treatment for advanced HCC.
Supplementary Methods from A Phase I Study of KIN-3248, an Irreversible Small-molecule Pan-FGFR Inhibitor, in Patients with Advanced FGFR2/3-driven Solid Tumors
Authors: Garmezy Benjamin , Borad Mitesh J. , Bahleda Rastilav , Perez Cesar A. , Chen Li-Tzong , Kato Shumei , Oh Do-Youn , Severson Paul , Tam Betty Y. , Quah Cheng S. , Harding James J.
Published: April 2024

Inclusion Criteria, Exclusion Criteria, Dose Limiting Toxicity Criteria for First Cycle
HER2-Status: Ein agnostischer Biomarker als Wegweiser für die T-DXd-Ansprechrate
Authors: Pölcher Martin
Published: April 2024

Purpose: Trastuzumab deruxtecan (T-DXd) is a human epidermal growth factor 2 (HER2)-directed antibody-drug conjugate approved in HER2-expressing breast and gastric cancers and HER2-mutant non-small-cell lung cancer. Treatments are limited for other HER2-expressing solid tumors. Methods: This open-label phase II study evaluated T-DXd (5.4 mg/kg once every 3 weeks) for HER2-expressing (immunohistochemistry [IHC] 3+/2+ by local or central testing) locally advanced or metastatic disease after ≥1 systemic treatment or without alternative treatments. The primary end point was investigator-assessed confirmed objective response rate (ORR). Secondary end points included safety, duration of response, progression-free survival (PFS), and overall survival (OS). Results: At primary analysis, 267 patients received treatment across seven tumor cohorts: endometrial, cervical, ovarian, bladder, biliary tract, pancreatic, and other. The median follow-up was 12.75 months. In all patients, the ORR was 37.1% (n = 99; [95% CI, 31.3 to 43.2]), with responses in all cohorts; the median DOR was 11.3 months (95% CI, 9.6 to 17.8); the median PFS was 6.9 months (95% CI, 5.6 to 8.0); and the median OS was 13.4 months (95% CI, 11.9 to 15.5). In patients with central HER2 IHC 3+ expression (n = 75), the ORR was 61.3% (95% CI, 49.4 to 72.4), the median DOR was 22.1 months (95% CI, 9.6 to not reached), the median PFS was 11.9 months (95% CI, 8.2 to 13.0), and the median OS was 21.1 months (95% CI, 15.3 to 29.6). Grade ≥3 drug-related adverse events were observed in 40.8% of patients; 10.5% experienced adjudicated drug-related interstitial lung disease (ILD), with three deaths. Conclusion: Our study demonstrates durable clinical benefit, meaningful survival outcomes, and safety consistent with the known profile (including ILD) in pretreated patients with HER2-expressing tumors receiving T-DXd. Greatest benefit was observed for the IHC 3+ population. These data support the potential role of T-DXd as a tumor-agnostic therapy for patients with HER2-expressing solid tumors. Trial registration: ClinicalTrials.gov NCT04482309.
Prevalência e perfil de uso de cigarros eletrônicos em estudantes de medicina de uma capital do sul do Brasil
Authors: Garcia Pedro Luiz Belei , Sielski Jorge Daher Scander , Oliveira Luiz Victor Padoan de , Duarte Marcos Eduardo dos Santos , Miranda Iago Garcia , Ramos Pietro Ragi Garofani , Andrade Fabiana Antunes
Published: April 2024

INTRODUÇÃO: Os cigarros eletrônicos têm ganhado destaque no cenário social brasileiro nos últimos anos, especialmente entre os universitários. Esta ascensão suscita indagações acerca da incidência e dos potenciais efeitos do seu consumo entre estudantes de medicina. OBJETIVO: investigar a prevalência e caracterizar o perfil socioeconômico de estudantes de medicina que utilizam os dispositivos eletrônicos para fumar (DEFs), além de investigar o grau de dependência de cigarros eletrônicos, tempo de uso e os sintomas associados. METODOLOGIA: Trata-se de um estudo observacional transversal realizado com estudantes de medicina da cidade de Curitiba-PR, através da aplicação de um questionário autoaplicável via plataforma Google Forms. O questionário possuía perguntas sobre dados socioeconômicos, uso de cigarro eletrônico e frequência, aparecimento de sintomas, presença de ansiedade e escala de dependência de nicotina. O estudo foi aprovado pelo Comitê de ética e pesquisa da Universidade Positivo. RESULTADOS: Foram incluídos 562 participantes, em sua maioria mulheres, com média de idade de 22 anos. A prevalência de usuários de cigarros eletrônicos foi de 39,7%. Quanto ao perfil dos usuários, proporcionalmente, a maioria é de homens com renda superior a 10 salários-mínimos. Tosse e odinofagia foram os principais sintomas apresentados. 72,5% dos que utilizam DEFs se declararam ansiosos, além disso, 22,4% dos usuários apresentaram grau elevado ou muito elevado de dependência, o qual foi associado à presença de sintomas ao fumar (p=0,021) e a uma tendência a presença de ansiedade (p=0,056). CONCLUSÃO: Observamos uma elevada prevalência de uso de cigarros eletrônicos entre estudantes de medicina. Considerando taxa de dependência e a observada relação do uso de DEFs com a ansiedade, torna-se imperativo a implementação de campanhas de conscientização, além do aprimoramento das práticas regulatórias referentes à sua comercialização e uso.
Estudo radiológico da prono-supinação do antebraço
Authors: Rossi João Alvarenga
Published: April 2024

O autor apresenta um método prático para caracterizar a posição relativa de prono-supinação entre o cúbito e o rádio, como medida para facilitar as manobras na redução das fraturas diafisárias dos ossos do antebraço e cria o conceito radiológico das imagens do A, do Y e do X.
Spatiotemporal ATF3 Expression Determines VSMC Fate in Abdominal Aortic Aneurysm
Authors: Wen Ying , Liu Yingying , Li Qiang , Tan Jinlin , Fu Xing , Liang Yiwen , Tuo Yonghua , Liu Luhao , Zhou Xueqiong , LiuFu Dongkai , Fan Xuejiao , Chen Chaofei , Chen Zheng , Wang Zhouping , Fan Shunyang , Liu Renjing , Pan Lei , Zhang Yuan , Tang Wai Ho
Published: April 2024

BACKGROUND:

Abdominal aortic aneurysm (AAA) is a catastrophic disease with little effective therapy, likely due to the limited understanding of the mechanisms underlying AAA development and progression. ATF3 (activating transcription factor 3) has been increasingly recognized as a key regulator of cardiovascular diseases. However, the role of ATF3 in AAA development and progression remains elusive.

METHODS:

Genome-wide RNA sequencing analysis was performed on the aorta isolated from saline or Ang II (angiotensin II)–induced AAA mice, and ATF3 was identified as the potential key gene for AAA development. To examine the role of ATF3 in AAA development, vascular smooth muscle cell–specific ATF3 knockdown or overexpressed mice by recombinant adeno-associated virus serotype 9 vectors carrying ATF3, or shRNA-ATF3 with SM22α (smooth muscle protein 22-α) promoter were used in Ang II–induced AAA mice. In human and murine vascular smooth muscle cells, gain or loss of function experiments were performed to investigate the role of ATF3 in vascular smooth muscle cell proliferation and apoptosis.

RESULTS:

In both Ang II–induced AAA mice and patients with AAA, the expression of ATF3 was reduced in aneurysm tissues but increased in aortic lesion tissues. The deficiency of ATF3 in vascular smooth muscle cell promoted AAA formation in Ang II–induced AAA mice. PDGFRB (platelet-derived growth factor receptor β) was identified as the target of ATF3, which mediated vascular smooth muscle cell proliferation in response to TNF-alpha (tumor necrosis factor-α) at the early stage of AAA. ATF3 suppressed the mitochondria-dependent apoptosis at the advanced stage by upregulating its direct target BCL2. Our chromatin immunoprecipitation results also demonstrated that the recruitment of NFκB1 and P300/BAF/H3K27ac complex to the ATF3 promoter induces ATF3 transcription via enhancer activation. NFKB1 inhibitor (andrographolide) inhibits the expression of ATF3 by blocking the recruiters NFKB1 and ATF3-enhancer to the ATF3-promoter region, ultimately leading to AAA development.

CONCLUSIONS:

Our results demonstrate a previously unrecognized role of ATF3 in AAA development and progression, and ATF3 may serve as a novel therapeutic and prognostic marker for AAA.
Atherosclerosis Is a Smooth Muscle Cell–Driven Tumor-Like Disease
Authors: Pan Huize , Ho Sebastian E. , Xue Chenyi , Cui Jian , Johanson Quinian S. , Sachs Nadja , Ross Leila S. , Li Fang , Solomon Robert A. , Connolly E. Sander , Patel Virendra I. , Maegdefessel Lars , Zhang Hanrui , Reilly Muredach P.
Published: April 2024

BACKGROUND:

Atherosclerosis, a leading cause of cardiovascular disease, involves the pathological activation of various cell types, including immunocytes (eg, macrophages and T cells), smooth muscle cells (SMCs), and endothelial cells. Accumulating evidence suggests that transition of SMCs to other cell types, known as phenotypic switching, plays a central role in atherosclerosis development and complications. However, the characteristics of SMC-derived cells and the underlying mechanisms of SMC transition in disease pathogenesis remain poorly understood. Our objective is to characterize tumor cell–like behaviors of SMC-derived cells in atherosclerosis, with the ultimate goal of developing interventions targeting SMC transition for the prevention and treatment of atherosclerosis.

METHODS:

We used SMC lineage tracing mice and human tissues and applied a range of methods, including molecular, cellular, histological, computational, human genetics, and pharmacological approaches, to investigate the features of SMC-derived cells in atherosclerosis.

RESULTS:

SMC-derived cells in mouse and human atherosclerosis exhibit multiple tumor cell–like characteristics, including genomic instability, evasion of senescence, hyperproliferation, resistance to cell death, invasiveness, and activation of comprehensive cancer-associated gene regulatory networks. Specific expression of the oncogenic mutant

Kras
G12D

in SMCs accelerates phenotypic switching and exacerbates atherosclerosis. Furthermore, we provide proof of concept that niraparib, an anticancer drug targeting DNA damage repair, attenuates atherosclerosis progression and induces regression of lesions in advanced disease in mouse models.

CONCLUSIONS:

Our findings demonstrate that atherosclerosis is an SMC-driven tumor-like disease, advancing our understanding of its pathogenesis and opening prospects for innovative precision molecular strategies aimed at preventing and treating atherosclerotic cardiovascular disease.
Unconstrained quantitative magnetization transfer imaging: Disentangling T1 of the free and semi-solid spin pools
Authors: Assländer Jakob , Mao Andrew , Marchetto Elisa , Beck Erin S. , Rosa Francesco La , Charlson Robert W. , Shepherd Timothy M. , Flassbeck Sebastian
Published: April 2024

Since the inception of magnetization transfer (MT) imaging, it has been widely assumed that Henkelman’s two spin pools have similar longitudinal relaxation times, which motivated many researchers to constrain them to each other. However, several recent publications reported a T1s of the semi-solid spin pool that is much shorter than T1f of the free pool. While these studies tailored experiments for robust proofs-of-concept, we here aim to quantify the disentangled relaxation processes on a voxel-by-voxel basis in a clinical imaging setting, that is, with an effective resolution of 1.24mm isotropic and full brain coverage in 12min. To this end, we optimized a hybrid-state pulse sequence for mapping the parameters of an unconstrained MT model. We scanned four people with relapsing-remitting multiple sclerosis (MS) and four healthy controls with this pulse sequence and estimated T1f≈1.84s and T1s≈0.34s in healthy white matter. Our results confirm the reports that T1s≪T1f and we argue that this finding identifies MT as an inherent driver of longitudinal relaxation in brain tissue. Moreover, we estimated a fractional size of the semi-solid spin pool of m0s≈0.212, which is larger than previously assumed. An analysis of T1f in normal-appearing white matter revealed statistically significant differences between individuals with MS and controls.
Symeon the New Theologian and The Life of St. Nephon of Constantiane (BHG 1371z)
Authors: Ivanov Sergey A.
Published: April 2024

The Life of St. Nephon (BHG 1371z) has been written between 970 and 992 and became extremely popular immediately after its publication. Therefore, it could become accessible to Symeon the New Theologian very soon after his conversion to spiritual life. The peculiar combination of ecstatic confessions of abominable sins and the simultaneous confidence in his divine chosenness, characteristic of the Life of Nephon, influenced Symeon and became the main style of self-representation in his writings.
An Early Renaissance Hebrew Alchemical Treatise in French Translation (ca. 1540)?
Authors: Kahn Didier , Freudenthal Gad
Published: April 2024

A manuscript, bearing the title Petit traicté de alkimie tourné de langue hebraique en langue francoyse, containing a collection of technical and alchemical recipes allegedly translated from Hebrew, was once donated by the Connétable Anne of Montmorency to his master, the French King François I. Our purpose is to examine whether or not the text indeed goes back to a Hebrew original. We first summarize the manuscript’s history, then examine the modern attribution of the text to Paul Paradis (or Paolo Canossa, 1511–1549), a well-known Hebraist appointed Royal Lecturer in 1530 by King François I. We finally turn to the contents of the Petit traicté de alkimie, and offer our conclusions as to its alleged Hebrew original. In an Appendix we offer a transcription of the entire text of the Petit traicté de alkimie.
Different microbial ecological agents change the composition of intestinal microbiota and the levels of SCFAs in mice to alleviate loperamide-induced constipation
Authors: Zhang C. , Wang L. , Liu X. , Wang G. , Guo X. , Liu X. , Zhao J. , Chen W.
Published: April 2024

Probiotics exert beneficial effects by regulating the intestinal microbiota, metabolism, immune function and other ways of their host. Patients with constipation, a common gastrointestinal disorder, experience disturbances in their intestinal microbiota. In the present study, we investigated the effectiveness of two microbial ecological agents (postbiotic extract PE0401 and a combination of postbiotic extract PE0401 and Lacticaseibacillus paracasei CCFM 2711) in regulating the makeup of the intestinal microbiota and alleviating loperamide hydrochloride-induced constipation in mice. We also preliminarily explored the mechanism underlying their effects. Both microbial ecological agents increased the abundance of the beneficial bacteria Lactobacilli and Bifidobacterium after administration and were able to relieve constipation. However, the degree of improvement in constipation symptoms varied depending on the makeup of the supplement. The postbiotic extract PE0401 increased peristalsis time and improved faecal properties throughout the intestinal tract of the host. PE0401 relieved constipation, possibly by modulating the levels of the constipation-related gastrointestinal regulatory transmitters mouse motilin, mouse vasoactive intestinal peptide, and 5-hydoxytryptamine in the intestinal tract of the host and by increasing the levels of the short-chain fatty acids (SCFAs) acetic acid, propionic acid, and isovaleric acid. It also increased the relative abundance of Lactobacillus and Bifidobacterium and reduced that of Faecalibaculum, Mucispirillum, Staphylococcus, and Lachnoclostridium, which are among the beneficial microbiota in the host intestine. Furthermore, PE0401 decreased the levels of constipation-induced host inflammatory factors. Therefore, the two microbial ecological agents can regulate the intestinal microbiota of constipation mice, and PE0401 has a stronger ability to relieve constipation.