bluuebunny/crossref_metadata_2025 huggingface dataset:
Deciphering prefrontal circuits underlying stress and depression: exploring the potential of volume electron microscopy
Authors: Nagai Hirotaka
Published: July 2024

Adapting to environmental changes and formulating behavioral strategies are central to the nervous system, with the prefrontal cortex being crucial. Chronic stress impacts this region, leading to disorders including major depression. This review discusses the roles for prefrontal cortex and the effects of stress, highlighting similarities and differences between human/primates and rodent brains. Notably, the rodent medial prefrontal cortex is analogous to the human subgenual anterior cingulate cortex in terms of emotional regulation, sharing similarities in cytoarchitecture and circuitry, while also performing cognitive functions similar to the human dorsolateral prefrontal cortex. It has been shown that chronic stress induces atrophic changes in the rodent mPFC, which mirrors the atrophy observed in the subgenual anterior cingulate cortex and dorsolateral prefrontal cortex of depression patients. However, the precise alterations in neural circuitry due to chronic stress are yet to be fully unraveled. The use of advanced imaging techniques, particularly volume electron microscopy, is emphasized as critical for the detailed examination of synaptic changes, providing a deeper understanding of stress and depression at the molecular, cellular and circuit levels. This approach offers invaluable insights into the alterations in neuronal circuits within the medial prefrontal cortex caused by chronic stress, significantly enriching our understanding of stress and depression pathologies.
Adverse events in men with advanced prostate cancer treated with androgen biosynthesis inhibitors and androgen receptor inhibitors
Authors: Faraj Kassem S , Oerline Mary , Kaufman Samuel R , Dall Christopher , Srivastava Arnav , Caram Megan E V , Shahinian Vahakn B , Hollenbeck Brent K
Published: July 2024

Background

The use of androgen biosynthesis and second-generation androgen receptor inhibitors for advanced prostate cancer is increasing. Because these therapies alter the androgen pathway, they have been associated with cardiometabolic and neurocognitive toxicities. Although their safety profiles have been assessed in clinical trials, real-world data are limited.

Methods

A 20% sample of national Medicare claims was used to perform a retrospective cohort study of Medicare beneficiaries with advanced prostate cancer treated with androgen biosynthesis (ie, abiraterone) and second-generation androgen receptor inhibitors between 2012 and 2019. Outcomes were assessed after the first fill of either class of drug for the 12-month period after starting therapy. The primary outcome was a hospital admission or emergency department visit for a cardiometabolic event. Secondary outcomes included neurocognitive events and fractures. Multivariable regression was used to assess the association between the class of drug and occurrence of an adverse event.

Results

There were 3488 (60%) men started on an androgen biosynthesis inhibitor and 2361 (40%) started on an androgen receptor inhibitor for the first time. Cardiometabolic adverse events were more common in men managed with androgen biosynthesis inhibitor (9.2% vs 7.5%, P = .027). No difference between androgen biosynthesis and androgen receptor inhibitors was observed for neurocognitive events (3.3% vs 3.4%, respectively; P = .71) or fractures (4.2% vs 3.6%, respectively; P = .26).

Conclusions

Men with advanced prostate cancer initiating an androgen biosynthesis inhibitor for the first time more commonly had cardiometabolic events than those started on androgen receptor inhibitors. Neurocognitive events and fractures did not differ by drug class.
Variation to biology: optimizing functional analysis of cancer risk variants
Authors: Nelson Stefanie , Carrick Danielle , Daee Danielle , Fingerman Ian , Gillanders Elizabeth
Published: July 2024

Research conducted over the past 15+ years has identified hundreds of common germline genetic variants associated with cancer risk, but understanding the biological impact of these primarily non-protein coding variants has been challenging. The National Cancer Institute sought to better understand and address those challenges by requesting input from the scientific community via a survey and a 2-day virtual meeting, which focused on discussions among participants. Here, we discuss challenges identified through the survey as important to advancing functional analysis of common cancer risk variants: 1) When is a variant truly characterized; 2) Developing and standardizing databases and computational tools; 3) Optimization and implementation of high-throughput assays; 4) Use of model organisms for understanding variant function; 5) Diversity in data and assays; and 6) Creating and improving large multidisciplinary collaborations. We define these 6 challenges, describe how success in addressing them may look, propose potential solutions, and note issues that span all the challenges. Implementation of these ideas could help develop a framework for methodically analyzing common cancer risk variants to understand their function and make effective and efficient use of the wealth of existing genomic association data.
Racial and ethnic disparities in robot-assisted radical prostatectomy: testing the physician-level segregated and differential treatment hypotheses
Authors: Mao Jialin , Genkinger Jeanine M , Rundle Andrew G , Wright Jason D , Insaf Tabassum Z , Schymura Maria J , Hu Jim C , Tehranifar Parisa
Published: July 2024

Background

Mechanisms underlying racial and ethnic disparities in robot-assisted radical prostatectomy (RARP) vs open radical prostatectomy (ORP) are unclear. We sought to test 2 physician-level hypotheses: 1) Segregated Treatment and 2) Differential Treatment.

Methods

This observational study used the New York State Cancer Registry linked to discharge records and included patients undergoing radical prostatectomy for localized prostate cancer from October 1, 2008 to December 31, 2018. For hypothesis 1, we examined the association between patient race and ethnicity and treating surgeon RARP use (high-use surgeons, low-use surgeons, and surgeons at non-RARP facilities). For hypothesis 2, we determined the association between patient race and ethnicity and receipt of RARP when matching on treating surgeon, age, year of procedure, and Gleason group. We explored the role of insurance in both analyses.

Results

This study included 18 926 patients (8.0% Hispanic, 16.9% non-Hispanic Black, 75.1% non-Hispanic White), with a mean age of 60.4 ± 7.1 years. Compared with non-Hispanic White patients, Hispanic and non-Hispanic Black patients had higher odds of being treated by low-RARP-use surgeons (odds ratio [OR] = 2.16, 95% confidence interval [CI] = 1.20 to 3.88; OR = 1.76, 95% CI = 1.06 to 2.94, respectively) and by surgeons at non-RARP facilities (OR = 4.19, 95% CI = 2.18 to 8.07; OR = 4.60, 95% CI = 2.58 to 8.23, respectively). In the matched cohorts, Hispanic and non-Hispanic Black patients were less likely to receive RARP than non-Hispanic White patients (OR = 0.78, 95% CI = 0.62 to 0.98; OR = 0.75, 95% CI = 0.57 to 1.00, respectively). These associations were partially attenuated after accounting for insurance.

Conclusions

Racial and ethnic disparities in RARP use are related to patients being treated by different surgeons and treated differently by the same surgeons. Identifying and addressing multilevel barriers to equitable surgical treatment is needed to reduce disparities among prostate cancer patients.
Dihydroisotanshinone I regulates ferroptosis via PI3K/AKT pathway to enhance cisplatin sensitivity in lung adenocarcinoma
Authors: Li Feng-Jiao , Gao Li-Chen , Long Hui-Zhi , Zhou Zi-Wei , Luo Hong-Yu , Xu Shuo-Guo , Dai Shang-Ming , Hu Jin-Da
Published: July 2024

Objectives

Dihydroisotanshinone I (DT) is a kind of diterpenoid compound extracted from the dried roots of Salvia miltiorrhiza Bunge, and exhibits multiple biological activities including anti-tumor activity. Cisplatin is one of the first-line drugs for the treatment of lung adenocarcinoma (LAUD), but the drug resistance and toxicity limit its efficacy. DT is known to induce apoptosis and ferroptosis, but it is unclear whether DT can inhibit the cisplatin-resistant LAUD cells and reverse the drug resistance in LAUD. Therefore, our study intends to establish the cisplatin-resistant human LAUD cells (A549/DDP), and figure out the influence and related mechanisms of DT reversing cisplatin resistance in A549/DDP cells, so as to provide a theoretical basis for the DT as a new natural candidate for the treatment of LAUD.

Methods

The establishment of A549/DDP was the continuous stimulation by exposing A549 to gradient concentrations of Cisplatin. The cell viability of A549 and A549/DDP was detected by CCK-8 kit, and the IC50 value was calculated. The morphological changes of A549 and A549/DDP cells were observed by an inverted microscope. The contents of malondialdehyde (MDA) and glutathione (GSH) in A549/DDP cells after drug treatment were detected by related kits. The levels of Fe2+, cytosolic reactive oxygen species (ROS), and lipid reactive oxygen species (lipid ROS) were detected by a fluorescence microplate reader or fluorescence cell imager according to the related fluorescent probe kit instructions. Western blot was used to detect the expressions of PI3K, phospho-PI3K, AKT, phospho-AKT, MDM2, p53, GPX4, and SLC7A11 in A549/DDP after different drug treatments.

Key findings

Our study demonstrated that the inhibitory effect of DT on A549 and A549/DDP cells was time-dependent and concentration-dependent, and DT and DDP had a synergistic effect on inhibiting the proliferation of A549/DDP cells. Furthermore, DT mainly induced ferroptosis in A549/DDP cells and synergized with cisplatin to promote ferroptosis in A549/DDP cells. The result of KEGG pathway analysis, molecular docking and western blot showed that DT could enhance the cisplatin sensitivity of A549/DDP by inhibiting PI3K/MDM2/P53 signaling pathway.

Conclusions

Consequently, we concluded that DT promotes ferroptosis in cisplatin-resistant LAUD A549/DDP cells. Additionally, DT reverses cisplatin resistance by promoting ferroptosis via PI3K/MDM2/P53 pathway in A549/DDP cells.
Co-administration of Ceratonia siliqua extract nanoparticles promotes the oral bioavailability and neurotherapeutic efficacy of donepezil in a dementia model
Authors: Shaker Sylvia E , Fayed Dalia B , Shawky Heba , Farrag Ebtehal K
Published: July 2024

Background

This study aimed to assess the herb–drug interactions between crude/silver nanoparticle (SNP)-loaded carob extract (Car, NCar, respectively) and donepezil-HCl (DPZ) and their impact on neurotherapeutic outcomes in a dementia model.

Methods

Carob pods were subjected to ethanol extraction, and their phytoconstituents were chromatographically analysed. SNP-loaded extract was synthesized and characterized, and dementia-like symptoms were induced in Wistar rats by repeated dosing with 175 mg/kg AlCl3 for 60 days, after which the animals were treated with Car, NCar, DPZ, and combinations of Car/NCar-DPZ for 30 days. The effect of carob formulations on DPZ bioavailability was in-silico profiled and the herb–drug interactions were mathematically assessed as combination indices.

Results

Different formulations significantly improved cognitive/spatial memory functions, restored dysregulated brain redox and cholinergic functions, and markedly inhibited cholinesterase, as reflected by the reduction/absence of amyloid plaques and neurofibrillary tangles. In silico profiling of the major phytoconstituents revealed their non-P-glycoprotein substrate nature and CYP3A4, 2C19, and 2C9 inhibition, which might have improved the oral bioavailability of DPZ. The combination index calculations revealed strong synergy between DPZ and both carob formulations, with the strongest effect exhibited by the DPZ/NCar combination.

Conclusion

The co-administration of carob extract/SNPs represents a promising approach for enhancing the neurotherapeutic efficacy of DPZ.
Tracking trend output using expectations data
Authors: Lee Kevin , Mahony Michael
Published: July 2024

This article proposes a new approach to measuring trend output that exploits survey data on expectations to distinguish the effects of permanent and transitory shocks and to track the time-variation in the processes underlying the determination of output. The approach is illustrated using measures of output expectations and output uncertainties based on a business survey conducted for UK manufacturing. The measures are employed in a time-varying vector autoregression (VAR) to track trend output and to provide a compelling characterization of the output fluctuations in UK manufacturing over the last 20 years.
Bias and excess variance in election polling: a not-so-hidden Markov model
Authors: Tierney Graham , Volfovsky Alexander
Published: July 2024

With historic misses in the 2016 and 2020 US Presidential elections, interest in measuring polling errors has increased. The most common method for measuring directional errors and non-sampling excess variability during a postmortem for an election is by assessing the difference between the poll result and election result for polls conducted within a few days of the day of the election. Analysing such polling error data is notoriously difficult with typical models being extremely sensitive to the time between the poll and the election. We leverage hidden Markov models traditionally used for election forecasting to flexibly capture time-varying preferences and treat the election result as a peek at the typically hidden Markovian process. Our results are much less sensitive to the choice of time window, avoid conflating shifting preferences with polling error, and are more interpretable despite a highly flexible model. We demonstrate these results with data on polls from the 2004 through 2020 US Presidential elections and 1992 through 2020 US Senate elections, concluding that previously reported estimates of bias in Presidential elections were too extreme by 10%, estimated bias in Senatorial elections was too extreme by 25%, and excess variability estimates were also too large.
Genomic and cell-specific regulation of benzylisoquinoline alkaloid biosynthesis in opium poppy
Authors: Hong Uyen Vu Thuy , Tamiru-Oli Muluneh , Hurgobin Bhavna , Lewsey Mathew G
Published: July 2024

Opium poppy is a crop of great commercial value as a source of several opium alkaloids for the pharmaceutical industries including morphine, codeine, thebaine, noscapine, and papaverine. Most enzymes involved in benzylisoquinoline alkaloid (BIA) biosynthesis in opium poppy have been functionally characterized, and opium poppy currently serves as a model system to study BIA metabolism in plants. BIA biosynthesis in opium poppy involves two biosynthetic gene clusters associated respectively with the morphine and noscapine branches. Recent reports have shown that genes in the same cluster are co-expressed, suggesting they might also be co-regulated. However, the transcriptional regulation of opium poppy BIA biosynthesis is not well studied. Opium poppy BIA biosynthesis involves three cell types associated with the phloem system: companion cells, sieve elements, and laticifers. The transcripts and enzymes associated with BIA biosynthesis are distributed across cell types, requiring the translocation of key enzymes and pathway intermediates between cell types. Together, these suggest that the regulation of BIA biosynthesis in opium poppy is multilayered and complex, involving biochemical, genomic, and physiological mechanisms. In this review, we highlight recent advances in genome sequencing and single cell and spatial transcriptomics with a focus on how these efforts can improve our understanding of the genomic and cell-specific regulation of BIA biosynthesis. Such knowledge is vital for opium poppy genetic improvement and metabolic engineering efforts targeting the modulation of alkaloid yield and composition.
Jasmonate/ethylene- and NaWRKY6/3-regulated Alternaria resistance depends on ethylene response factor 1B-like in Nicotiana attenuata
Authors: Ma Lan , Song Na , Duan Qing , Du Wenwen , Li Xiang , Jia Wenjie , Cui Guangfen , Wang Jihua , Wu Jinsong
Published: July 2024

Biosynthesis of the phytoalexins scopoletin and scopolin in Nicotiana species is regulated by upstream signals including jasmonate (JA), ethylene (ET), and NaWRKY3 in response to the necrotrophic fungus Alternaria alternata, which causes brown spot disease. However, how these signals are coordinated to regulate these phytoalexins remains unknown. By analyzing RNA sequencing data and RNAi, we identified NaERF1B-like (NaERF1B-L) as a key player in Nicotiana attenuata during A. alternata infection by regulating the transcripts of Feruloyl-CoA 6'-hydroxylase 1 (NaF6'H1), encoding a key enzyme for scopoletin biosynthesis, and NaVS1-like (NaVS1-L), a putative biosynthetic gene of the phytoalexin solavetivone. We further demonstrated that the synergistic induction of these two genes by JA and ET signaling is mediated by NaERF1B-L. Additionally, we found that the two closely related proteins, NaWRKY6 and NaWRKY3, physically interact to enhance NaERF1B-L expression by directly binding to and activating the NaERF1B-L promoter. Collectively, our current results demonstrate that NaERF1B-L plays a positive role in resistance to A. alternata by modulating phytoalexin biosynthesis through the integration of JA/ET and NaWRKY6/3 signaling. Our findings reveal a fine-tuned transcriptional regulatory hierarchy mediated by NaERF1B-L for brown spot disease resistance in wild tobacco.
Nuclear localization of Arabidopsis HD-Zip IV transcription factor GLABRA2 is driven by importin α
Authors: Ahmad Bilal , Lerma-Reyes Ruben , Mukherjee Thiya , Nguyen Hieu V , Weber Audra L , Cummings Emily E , Schulze Waltraud X , Comer Jeffrey R , Schrick Kathrin
Published: July 2024

GLABRA2 (GL2), a class IV homeodomain leucine-zipper (HD-Zip IV) transcription factor from Arabidopsis, is a developmental regulator of specialized cell types in the epidermis. GL2 contains a monopartite nuclear localization sequence (NLS) that is conserved in most HD-Zip IV members across the plants. We demonstrate that NLS mutations affect nuclear transport and result in a loss-of-function phenotypes. NLS fusions to enhanced yellow fluorescent protein (EYFP) show that it is sufficient for nuclear localization in roots and trichomes. Despite partial overlap of the NLS with the homeodomain, genetic dissection indicates that nuclear localization and DNA binding are separable functions. Affinity purification of GL2 from plants followed by MS-based proteomics identified importin α (IMPα) isoforms as potential GL2 interactors. NLS structural prediction and molecular docking studies with IMPα-3 revealed major interacting residues. Cytosolic yeast two-hybrid assays and co-immunoprecipitation experiments with recombinant proteins verified NLS-dependent interactions between GL2 and several IMPα isoforms. IMPα triple mutants (impα-1,2,3) exhibit abnormal trichome formation and defects in GL2 nuclear localization in trichomes, consistent with tissue-specific and redundant functions of IMPα isoforms. Taken together, our findings provide mechanistic evidence for IMPα-dependent nuclear localization of GL2 in Arabidopsis, a process that is critical for cell type differentiation of the epidermis.
Ulcerative colitis
Authors: Grieco Michael J. , Remzi Feza H.
Published: July 2024

Surgery plays an important role in the multidisciplinary care of ulcerative colitis as resection of the colon and rectum cures their symptoms. Reconstructive endpoints after resection of the colon and rectum, are conventional end ileostomy, continent ileostomy, or ileal pouch anal anastomosis (IPAA), of which IPAA is the gold standard. We describe a three-stage procedure for IPAA with total abdominal colectomy with end ileostomy as stage 1, proctectomy IPAA with loop ileostomy creation as stage 2, and hand-sewn ileostomy as stage 3. If after ileostomy closure, a patient requires diversion, we recommend creating a thoughtful ileostomy 20 cm proximal to the pouch. This can be a valuable step toward pouch salvage.
Head and Neck
Authors: Morchi Ravi
Published: July 2024

The chapter starts with clinically relevant soft tissue and neurovascular anatomy of the neck. Commonly tested ocular and otologic terms are outlined. The approach to nasal cavity and oral cavity pathology, particularly neoplasia, is next. The pharynx is reviewed in detail, with a focus on nasopharynx, oropharynx, and hypopharynx malignancy. The architecture and corresponding pathology of the larynx occupies its own section, followed by a description of highly tested salivary gland tumors. The chapter closes with the diagnostic approach to a new neck mass geared toward the board examination.
Neurological complications of radiation therapies in haematological malignancies
Authors: Winter Sebastian F. , Dietrich Jorg
Published: July 2024

Cranial radiation therapy is an integral treatment component in patients with haematological malignancies, but exposure of nervous system structures to ionizing radiation may result in a range of significant neurological complications. Patients with haematological malignancies, many of whom are long-term survivors with a remote history of antineoplastic therapy during childhood, are particularly susceptible to developing late radiogenic sequelae. Late-delayed neurological radiotoxicities are typically progressive and irreversible, difficult to diagnose and manage, and may permanently compromise neurological function with potentially detrimental effects on quality of life and survivorship. This chapter offers a comprehensive review of the most common and challenging forms of late central and peripheral nervous system radiotoxicities encountered in this patient population, with a focus on the most relevant preventative, diagnostic, and management considerations for practising clinicians.
General anatomy
Authors: Koshi Rachel
Published: July 2024

General anatomy is common to all regions of the body (head, neck, trunk, and limbs). This chapter introduces a vocabulary to define the positions of each anatomical structure, and an elementary knowledge of the types of structures a student of medicine, dentistry, or allied health sciences will encounter. Terms of position (e.g. anterior, posterior) and terms of movement (e.g. flexion, extension) are provided and explained. An overview of the skeletal system, including bones, cartilages, and joints, is outlined. Endochondral ossification and intramembranous ossification are explained. Readers are introduced to muscles, their component parts, types, classification, and naming, and much more. The skin, fascia, circulatory system, lymphatic system, and nervous system are all introduced, in turn. Many medical students will undertake dissection on cadavers as an important way of getting a fuller understanding of the structure and function of the human body. The chapter outlines general instructions for dissection. Lastly, special radiological techniques which allow the study of bones are introduced, including X-rays, computerized tomography (CT), ultrasound, and magnetic resonance imaging (MRI).
Introduction to the upper limb
Authors: Koshi Rachel
Published: July 2024

The introduction to the upper limb gives an overview of the upper limb. It defines the regions of the upper limb—the shoulder region, axilla, pectoral region, scapular region, arm or brachium, forearm or antebrachium, wrist, hand, and digits. For each region it describes the bones and muscle groups, including the muscle groups in the palm of the hand. It names the joints of the upper limb detailing the bones that come to together to articulate in each. In addition, this chapter describes how the upper limb relates to the adjacent structures in the body, namely the neck and thorax.
The free upper limb
Authors: Koshi Rachel
Published: July 2024

The free upper limb describes the general features of the arm, forearm, wrist, and hand. It begins with the bony landmarks and the surface features of this region. It describes the cutaneous nerves, superficial veins, and lymphatics, with attention to the origin, course, and termination of each. A concise overview of all the cutaneous nerves on the arm, forearm, and hand is provided. It describes the superficial fascia and deep fascia of the upper limb. Detailed, stepwise instructions are provided to enable the student to display the fascia, nerves, and vessels. Localized sensory loss due to damage to a peripheral nerve is discussed. The clinical importance of the superficial veins and possible complications of intravenous injection into the median cubital vein are discussed.
The arm
Authors: Koshi Rachel
Published: July 2024

This chapter describes the surface features of the arm, humerus, biceps brachii, triceps brachii, and other muscles, as they lie in the anterior and posterior intermuscular compartments. The nerves and blood vessels supplying these muscles, the musculocutaneous nerve, the radial nerve, the brachial artery, and their branches are described. The components forming the principal neurovascular bundle of the arm are listed. The location, boundaries, and contents of the cubital fossa are described. The chapter provides detailed instructions on how the arm should be dissected to display and study the structures. Descriptions and dissections are well illustrated. A common nerve injury complicating a fracture of the humerus and blood flow changes in the brachial artery during blood pressure measurement are discussed.
The forearm and hand
Authors: Koshi Rachel
Published: July 2024

This chapter on the forearm and hand describes the surface landmarks, the radius, the ulna, the carpals, metacarpals, and phalanges, the flexors of the wrist, the extensors of the wrist, the palmar aponeurosis, the flexor and extensor retinacula, the muscles of the hand, the median nerve, the ulnar nerve, the radial nerve, the anterior interosseous and posterior interosseous nerves, the radial artery, and the ulnar artery. The contents common to the anterior compartment of the forearm and palm of the hand are traced into continuity. Similarly, tendons, vessels, and nerves from the back of the forearm are traced onto the dorsum of the hand. All descriptions and dissections are well illustrated. Images on surface anatomy and cross-sectional images are used to illustrate the surface projections and interrelations between structures. The anatomy of common clinical conditions, such as carpal tunnel syndrome, tenosynovitis, and Dupuytren’s contraction, are discussed.
The gluteal region
Authors: Koshi Rachel
Published: July 2024

The gluteal region describes the surface features, bony landmarks, the gluteus maximus and other muscles of the gluteal region, and their nerves and arteries. The structures under cover of the gluteus maximus—gluteus medius, gluteus minimus, piriformis, the superior and inferior gluteal arteries, the superior and inferior gluteal nerves, the sciatic nerve, and the sacrotuberous ligament—are described. The boundaries of the greater sciatic notch and lesser sciatic notch are mentioned, and the structures passing through the greater and lesser sciatic foramina are described. Detailed, stepwise instructions are provided for dissecting this region. All descriptions and dissections are well illustrated. The gluteus medius gait and possible complications of a poorly administered intragluteal injection are discussed.
The back of the thigh
Authors: Koshi Rachel
Published: July 2024

This chapter describes the biceps femoris, semimembranosus, and semitendinosus muscles, the sciatic nerve, and the profunda femoris artery. It also describes the posterior cutaneous nerve of the thigh and the arterial anastomosis formed between the branches of the profunda femoris artery, the gluteal arteries, and the popliteal artery. Detailed, stepwise instructions are provided for dissecting this region. All descriptions and dissections are well illustrated. The clinical condition of sciatic neuritis is discussed.
The hip joint
Authors: Koshi Rachel
Published: July 2024

This chapter describes the acetabulum, the head of the femur, the neck of the femur, the articular capsule, extracapsular ligaments, intracapsular ligaments, and movements of the hip joint. Specializations of the articular capsule, such as the retinacula, and the thickenings that form the pubofemoral and iliofemoral ligaments are described. Important intracapsular structures, such as the ligament of the head of the femur and the acetabular labrum, are also described. The hip arterial supply is discussed. Detailed, stepwise instructions are provided for dissecting this joint. All descriptions and dissections are well illustrated. The hip joint movements and the origin, insertion, nerve supply, and action of the muscles producing them are tabulated for easy reference. A clinical case of a fractured neck of the femur treated with hemiarthroplasty is presented with radiological images.
The leg and foot
Authors: Koshi Rachel
Published: July 2024

This chapter describes the bones, muscles, vessels, and nerves of the leg and foot. It discusses the superficial veins of the leg and the communications between the deep and superficial veins. The structures in the leg are described in the three compartments: the front of the leg with the extensors of the ankle and toes, along with the deep fibular nerve and anterior tibial artery; the lateral side of the leg—the fibular compartment with the fibularis longus and brevis and the superficial fibular nerve; and the back of the leg with the gastrocnemius, soleus, long flexors, tibial nerve, and posterior tibial artery. The origin, course, relations, branches (or tributaries), termination of important nerves, and vessels of the anterior compartment of the leg are described. The dorsum of the foot and the sole of the foot are described. Detailed, stepwise instructions are provided for dissecting this region. All descriptions and dissections are well illustrated. Clinical anatomy of varicose veins of the leg, the anterior compartment syndrome, foot drop, and injury to the common fibular nerve are discussed.
Surface marking of the lower limb
Authors: Koshi Rachel
Published: July 2024

This chapter demonstrates the knowledge and skills to mark the position of important structures of the lower limb on to the surface of the body. Surface markings of clinically important structures include the mid-inguinal point, saphenous opening, long saphenous vein, short saphenous vein, femoral artery, popliteal artery, posterior tibial artery, anterior tibial artery, dorsalis pedis artery, femoral nerve, sciatic nerve, tibial nerve, common peroneal nerve, and deep peroneal nerve. Illustrations demonstrate the relevant bony and soft tissue landmarks, so readers can mark the structures on the surface of the body. The chapter outlines the surface marking competencies for the lower limb required by the National Medical Council of India curricula.
Knowledge production in refugee studies from the South: Theorization of refugee labour in the literature on Turkey
Authors: Osseiran Souad , Nimer Maissam
Published: July 2024

This article explores the case of the migration studies industry in Turkey, which has flourished over the past decade, through an examination of knowledge production on refugee labour. Focusing on research about Syrian refugees’ labour and employment in Turkey between 2012 and 2018, the article discusses the ways in which refugee labour is articulated and studied to provide ground for a wider critique of migration-related knowledge production. This study aims to reflexively question academic outputs by (1) exploring the conceptual frames used broadly in research on refugee labour, and (2) developing an overview of the literature on Turkey with a focus on this topic. Through the case of the literature on refugee labour in Turkey, we explore the underlying political economy premises of migration research. This case serves as an example to argue that knowledge produced in a Southern context is mainly incorporated as case studies despite attempts to advance theoretical discussions, highlighting a North–South hierarchization of knowledge.
Vinpocetine increases the microsporicidal effect of albendazole on Encephalitozoon intestinalis
Authors: Sezer Gülay , Çetinkaya Ülfet
Published: July 2024

Microsporidia are obligate, intracellular, spore-forming eukaryotic fungi that infect humans and animals. In the treatment of disseminated microsporidiosis albendazole is the choice of drug. In recent years, antiparasitic activity of phosphodiesterase (PDE) enzyme inhibitors has been demonstrated against parasites and fungi, however, there is no information on microsporidia. Vinpocetine is currently used as a cerebral vasodilator drug and also as a dietary supplement to improve cognitive functions. Vinpocetine inhibits PDE1, so we aimed to investigate whether vinpocetine alone or in combination with albendazole has any effect on the spore load of Encephalitozoon intestinalis (E. intestinalis)-infected HEK293 cells. After determining the noncytotoxic concentrations of vinpocetine and albendazole on the host cell by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, HEK293 cells were infected with E. intestinalis spores. Then, two different concentrations of vinpocetine, albendazole, and a combination of both drugs were applied to the cells with an interval of 72 h for 15 days. Spore load of the cells was analyzed by real-time PCR. After the last treatment, spore Deoxyribonucleic Acid (DNA) load was significantly reduced only in the group treated with 14 ng/ml albendazole. It was not different from control in groups treated with 7 ng/ml albendazole and 4–20 µM vinpocetine. However, the combination of vinpocetine significantly increased the effect of albendazole at both concentrations.

To our knowledge, this is the first study to investigate the microsporicidal activity of vinpocetine as well as its combinations with albendazole. However, further studies are needed to investigate the mechanism of action and also confirm in vivo conditions.
Time-variable diffuse γ-ray foreground
Authors: Siegert Thomas
Published: July 2024

While the data analysis of γ-ray telescopes has now become more robust, some signals may be misinterpretations of a time-variable foreground emission from the Solar system, induced by low-energy cosmic-ray interactions with asteroids. Our goal is to provide emission templates for this time-variable diffuse γ-ray foreground by considering the populations of Main Belt Asteroids, Jovian and Neptunian Trojans, Kuiper Belt Objects, and the Oort Cloud. We model the spatial distribution of all known asteroids by performing 3D-fits to determine their density profiles and calculate their appearances by line-of-sight integrations. Because Earth and the asteroids are moving with respect to each other, we obtain diffuse emission templates varying on time-scales of days to decades. We find that the temporal variability can lead to flux enhancements that may mimic emission features unless properly taken into account. This variation is further enhanced by the Solar cycle as the cosmic-ray spectrum is attenuated by the Solar modulation potential, leading to a relative flux increase of the outer asteroids. The cumulative effect of the time-dependent emission is illustrated for the case of the ‘511 keV OSSE fountain’, and for emission features near the Galactic Centre, both being possible misinterpretations of the Solar system albedo. We recommend that γ-ray data analyses should always take into account the possibility of a time-variable foreground. Due to the ecliptic overlap with the Galactic plane, the Galactic emission is expected to be weaker by 0.1–20 per cent, depending on time (relative planetary motion), energy, and Solar cycle, which has consequences for the interpretation of dark matter annihilation cross sections, cosmic-ray spectra and amplitudes, as well as nucleosynthesis yields and related parameters.
Long-term wide-band spectrotemporal studies of outbursting black hole candidate sources GX 339–4 and H 1743–322: AstroSat and NuSTAR results
Authors: Aneesha U , Das Santabrata , Katoch Tilak B , Nandi Anuj
Published: July 2024

We present a comprehensive spectrotemporal analyses of recurrent outbursting black hole sources GX 339$-$4 and H 1743$-$322 using available AstroSat and NuSTAR archival observations during 2016–2024. The nature of the outburst profiles of both sources are examined using long-term MAXI/GSC and Swift/BAT light curves, and failed as well as successful outbursts are classified. Wide-band (0.5–60 keV) spectral modelling with disc (diskbb) and Comptonized (Nthcomp) components indicates that GX 339$-$4 transits from hard ($kT_{\rm bb}=0.12-0.77$ keV, $\Gamma _{\rm nth}=1.54-1.74$, and $L_{\rm bol}=0.91-11.56$ per cent $L_{\rm Edd}$) to soft state ($kT_{\rm in}~[\approx {kT}_{\rm bb}]=0.82-0.88$ keV, $\Gamma _{\rm nth}=1.46-3.26$, $L_{\rm {bol}}=19.59-30.06~{{\ \rm per\ cent}}L_{\rm Edd}$) via intermediate state ($kT_{\rm in}~[\approx {kT}_{\rm {bb}}]=0.56-0.88$ keV, $\Gamma _{\rm nth}=1.76-2.66$, $L_{\rm {bol}}=2.90-16.09~{{\ \rm per\ cent}}L_{\rm Edd}$), whereas H 1743$-$322 transits from quiescent to hard state ($\Gamma _{\rm nth}=1.57-1.71$, $L_{\rm {bol}}=2.08-3.48~{{\ \rm per\ cent}}L_{\rm Edd}$). We observe type-B and type-C quasi-periodic oscillations (QPOs) in GX 339$-$4 with increasing frequencies ($0.10 - 5.37$ Hz) along with harmonics. For H 1743$-$322, prominent type-C QPOs are observed in frequency range 0.22–1.01 Hz along with distinct harmonics. Energy-dependent power spectral studies reveal that fundamental QPO and harmonics disappear beyond 20 keV in GX 339$-$4, whereas fundamental QPO in H 1743$-$322 persists up to 40 keV. We also observe that type-C ${\rm QPO}_{\rm rms}\,\rm per\,cent$ decreases with energy for both sources although such variations appear marginal for type-B QPOs. Additionally, we report non-monotonic behaviour of photon index with plasma temperature and detection of annihilation line. Finally, we discuss the relevance of the observational findings in the context of accretion dynamics around black hole binaries.
A flux-independent increase in outflows prior to the emergence of active regions on the Sun
Authors: Schunker H , Roland-Batty W , Birch A C , Braun D C , Cameron R H , Gizon L
Published: July 2024

Emerging active regions are associated with convective flows on the spatial scale and lifetimes of supergranules. To understand how these flows are involved in the formation of active regions, we aim to identify where active regions emerge in the supergranulation flow pattern. We computed supergranulation scale flow maps at the surface for all active regions in the Solar Dynamics Observatory Helioseismic Emerging Active Region Survey. We classified each of the active regions into four bins based on the amplitude of their average surface flow divergence at emergence. We then averaged the flow divergence over the active regions in each bin as a function of time. We also considered a corresponding set of control regions. We found that, on average, the flow divergence increases during the day prior to emergence at a rate independent of the amount of flux that emerges. By subtracting the averaged flow divergence of the control regions, we found that active region emergence is associated with a remaining converging flow at 0.5–1 d prior to emergence. This remnant flow, $\Delta \, \mathrm{div} \, \boldsymbol {v}_{\rm h} = (-4.9 \pm 1.7) \times 10^{-6}\,{\rm s}^{-1}$, corresponds to a flow speed of 10–20 m s−1 (an order of magnitude less than supergranulation flows) out to a radius of about 10 Mm. We show that these observational results are qualitatively supported by simulations of a small bipole emerging through the near-surface convective layers of the Sun. The question remains whether these flows are driving the emergence, or are caused by the emergence.
A physical model for radio and X-ray correlation in black hole X-ray binaries
Authors: Jiang Yiheng , Li Shanshan , Cao Xinwu , You Bei , Zdziarski Andrzej A , Xu Saien
Published: July 2024

A tight correlation between the radio and X-ray emission in the hard state of black hole X-ray binaries (BHXRBs) indicates an intrinsic disc–jet connection in stellar black hole (BH) accretion systems, though the detailed physics processes at work are still quite unclear. A hot accretion flow is suggested to match the outer cold thin disc at a certain radius in the hard state, which may vary with the accretion rate. In this work, we assume that the magnetic field generated in the outer thin disc is advected inwards by the inner hot accretion flow, which is substantially enhanced near the BH. Such a strong field threading the horizon of a spinning BH is responsible for launching relativistic jets in BHXRBs via the Blandford–Znajek mechanism. Thus, both the jet power and the X-ray emission increase with the mass accretion rate, and we find that our model calculations are able to reproduce the observed radio/X-ray correlation quantitatively. For some individual BHXRBs, the slopes of the radio/X-ray correlations become steeper when the sources are brighter. Our model calculations show that this feature is due to the transition of the outer disc from gas pressure dominated to radiation pressure dominated, which leads to different accretion rate dependence of the field strength in the outer disc.
The Fe Kα Compton shoulder in accreting supermassive black holes
Authors: Dimopoulos G , Ricci C , Paltani S
Published: July 2024

Reprocessed X-ray radiation from active galactic nuclei (AGN) carries important information about the properties of the circumnuclear material around the black hole. The X-ray photons travel from the very centre of the system and interact with that material often producing strong emission lines. The $\rm {Fe\, K\alpha }$ Compton shoulder (CS) is formed by fluorescent $\rm {Fe\, K\alpha }$ photons that perform Compton scatterings with the intercepting material and lose energy to form the distinct shoulder shape. In this work, we use the ray-tracing code RefleX to explore how the physical properties of the medium, as well as its geometry, affect the shape of the CS. We start by running simulations using a simple toroidal reflector, to test the effect of the metal composition, metallicity, column density, dust presence and velocity on the $\rm {Fe\, K\alpha }$ line, and its CS. We confirm that the shape of the CS is sensitive to the optical depth of the intercepting medium, which can be regulated by either changing the metal composition or the line-of-sight column density of the circumnuclear material. Next, we create a series of models, which feature different geometrical configurations of dust and gas, and explore how the CS is affected by such configurations finding that components that can regulate the line-of-sight column density affect the $\rm {Fe\, K\alpha }$ and its CS. Finally, we test whether observatories such as the recently launched XRISM and future Athena will make the CS a useful spectral feature of nearby AGN, by applying specific models on simulated spectra of the Circinus galaxy. The CS has the potential to be used to help constrain properties of the circumnuclear material yet with some limitations.
The obsidian model: three regimes of black hole feedback
Authors: Rennehan Douglas , Babul Arif , Moa Belaid , Davé Romeel
Published: July 2024

In theoretical models of galaxy evolution, black hole feedback is a necessary ingredient in order to explain the observed exponential decline in number density of massive galaxies. Most contemporary black hole feedback models in cosmological simulations rely on a constant radiative efficiency (usually $\eta \sim 0.1$) at all black hole accretion rates. We present the obsidian subgrid model, a synthesis model for the spin-dependent radiative efficiencies of three physical accretion rate regimes, i.e. $\eta = \eta (j, \dot{M}_\mathrm{acc})$, for use in large-volume cosmological simulations. The three regimes include: an advection-dominated accretion flow ($\dot{M}_\mathrm{acc}\lt 0.03\, \dot{M}_\mathrm{Edd}$), a quasar-like mode ($0.03 \lt \dot{M}_\mathrm{acc}/ \dot{M}_\mathrm{Edd}\lt 0.3$), and a slim disc mode ($\dot{M}_\mathrm{acc}\gt 0.3\, \dot{M}_\mathrm{Edd}$). Additionally, we include a large-scale powerful jet at low accretion rates. The black hole feedback model we present is a kinetic model that prescribes mass loadings but could be used in thermal models directly using the radiative efficiency. We implement the obsidian model into the simba galaxy evolution model to determine if it is possible to reproduce galaxy populations successfully, and provide a first calibration for further study. Using a $2\times 1024^3$ particle cosmological simulation in a $(150\, \mathrm{cMpc})^3$ volume, we found that the model is successful in reproducing the galaxy stellar mass function, black hole mass–stellar mass relationship, and stellar mass–halo mass relationship. Moving forward, this model opens new avenues for exploration of the impact of black hole feedback on galactic environments.
Towards modelling AR Sco: generalized particle dynamics and strong radiation-reaction regimes
Authors: Du Plessis L , Venter C , Harding A K , Wadiasingh Z , Kalapotharakos C , Els P
Published: July 2024

Numerical simulations of relativistic plasmas have become more feasible, popular, and crucial for various astrophysical sources with the availability of computational resources. The necessity for high-accuracy particle dynamics is especially highlighted in pulsar modelling due to the extreme associated electromagnetic fields and particle Lorentz factors. Including the radiation-reaction force in the particle dynamics adds even more complexity to the problem, but is crucial for such extreme astrophysical sources. We have also realized the need for such modelling concerning magnetic mirroring and particle injection models proposed for AR Sco, the first white dwarf pulsar. This paper demonstrates the benefits of using higher-order explicit numerical integrators with adaptive time-step methods to solve the full particle dynamics with radiation-reaction forces included. We show that for standard test scenarios, namely various combinations of uniform E- and B-fields and a static dipole B-field, the schemes we use are equivalent to and in extreme field cases outperform standard symplectic integrators in accuracy. We show that the higher-order schemes have massive computational time improvements due to the adaptive time-steps we implement, especially in non-uniform field scenarios and included radiation reaction where the particle gyro-radius rapidly changes. When balancing accuracy and computational time, we identified the adaptive Dormand–Prince eighth-order scheme to be ideal for our use cases. The schemes we use maintain accuracy and stability in describing the particle dynamics and we indicate how a charged particle enters radiation-reaction equilibrium and conforms to the analytical Aristotelian Electrodynamics expectations.