bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeted whole-genome recovery of single viral species in a complex environmental sample
Authors: Chen Liyin , Chen Anqi , Zhang Xinge Diana , Saenz Robles Maria Teresa , Han Hee-Sun , Xiao Yi , Xiao Gao , Pipas James M. , Weitz David A.
Published: July 2024

Characterizing unknown viruses is essential for understanding viral ecology and preparing against viral outbreaks. Recovering complete genome sequences from environmental samples remains computationally challenging using metagenomics, especially for low-abundance species with uneven coverage. We present an experimental method for reliably recovering complete viral genomes from complex environmental samples. Individual genomes are encapsulated into droplets and amplified using multiple displacement amplification. A unique gene detection assay, which employs an RNA-based probe and an exonuclease, selectively identifies droplets containing the target viral genome. Labeled droplets are sorted using a microfluidic sorter, and genomes are extracted for sequencing. We demonstrate this method’s efficacy by spiking two known viral genomes, Simian virus 40 (SV40, 5,243 bp) and Human Adenovirus 5 (HAd5, 35,938 bp), into a sewage sample with a final abundance in the droplets of around 0.1% and 0.015%, respectively. We achieve 100% recovery of the complete sequence of the spiked-in SV40 genome with uniform coverage distribution. For the larger HAd5 genome, we cover approximately 99.4% of its sequence. Notably, genome recovery is achieved with as few as one sorted droplet, which enables the recovery of any desired genomes in complex environmental samples, regardless of their abundance. This method enables single-genome whole-genome amplification and targeting characterizations of rare viral species and will facilitate our ability to access the mutational profile in single-virus genomes and contribute to an improved understanding of viral ecology.
Faith: A Very Short Introduction
Authors: Trigg Roger
Published: July 2024

What is faith? It usually means religious belief, and sometimes diverse religions are grouped together as faiths, with reference to ‘faith leaders’ or ‘faith schools’. What we have faith in matters, and that involves our reason, and claims to truth to that affect everyone. Faith is not just a personal attribute, like taste, but should be open to public examination and debate. Science in the modern age appears to many to provide a more certain basis for life together, particularly in the face of the competing beliefs of different religions. Science needs as much rational justification is any religion. This book argues that all faith needs reason. It puts contemporary discussions into historical perspective, particularly in the context of Christianity. Faith also involves a commitment to action. It matters for all social life. Because religion is typically directed at what is seen as of crucial importance for human life, faith should not be marginalized or privatized. It will permeate every idea of how people should behave, and has a role in the public sphere, however respectful it should be to competing views within democracy. It could have relevance for law, and Islam in particular, tends to emphasize obedience to divine law, instead of faith. A belief that does not result in appropriate action is empty. Acting without belief is unguided. All faith needs both.
Faith and law
Authors: Trigg Roger
Published: July 2024

Faith is not just private, because religious beliefs are manifested in public, and come within the ambit of public law. Freedom of religion is a basic right but can clash with other human rights. How special is religious faith? The United States Constitution certainly picked it out as of particular importance. What privileges can be claimed for religious faith, and even conscience in general? In a pluralist and democratic society, alternative views, and the freedom to live by them, must be fostered. Law should not coerce religious believers into doing what they believe is morally wrong. There are major problems about how far religious and civil law can coincide. This is a particular problem for Islam and sharia law. Different approaches to law show contrasts between Muslim and Christian views of faith.
Faith and society
Authors: Trigg Roger
Published: July 2024

In a secular society, there is often the assumption that faith is the antithesis of reason and can make no useful contribution to public debate. It is feared that faith encourages certainty, dogmatism, and intolerance. Differences in religious belief and moral priorities must be confronted. Discounting them fails to take any religion seriously. Any faith can still be confident in its own judgement, while respecting difference. It has to come to terms itself with doubt, while invoking a wholehearted commitment that affects the whole of life. We cannot be committed to what we recognize as false, but all faith involves the will, the imagination, and emotions, as well as the intellect. Any belief that does not result in appropriate action is empty. Acting without belief is unguided. All faith needs both.
Quantifying the Use of Space in the Clock Drawing Test: Validity in Hemispatial Neglect
Authors: Diana Lorenzo , Rusconi Maria Luisa , Aiello Edoardo Nicolò , Bolognini Nadia , Monti Alessia , Corbo Massimo , Sozzi Matteo
Published: July 2024

Objective

The Clock Drawing Test (CDT) is a widely used test for cognitive screening as its execution taps into a large number of cognitive functions. Because of the involvement of visuospatial abilities, the CDT is also commonly used to assess hemispatial neglect. In the present study, we introduce a new quantitative scoring method for the CDT that aims to measure the use of space for each half of the clock face and asymmetries of space use.

Method

Two measures are introduced: the explored space (ES) and used space (US) for each half of the clock, as well as two derived asymmetry indices. Such new measures were applied to CDTs of four groups of participants: right brain-damaged patients without visuospatial neglect, two groups of right brain-damaged patients with varying degrees of visuospatial neglect, and a group of neurologically healthy participants.

Results

Analyses showed that only neglect patients explored and used the left clock half significantly less than the right one. This result was also confirmed by the asymmetry indices, where neglect patients showed a stronger rightward bias. For neglect patients, the US asymmetry index correlated with the patients’ scores on the neuropsychological tests. The analyses of receiver operating characteristic curves showed that left US and left ES scores had good accuracy in categorizing neglect patients.

Conclusions

The present work provides new quantitative indices of CDT space usage in hemispatial neglect. Cutoffs are provided for clinical practice.
Recurrent oral and nasopharyngeal ulcers, facial erythema, vesicles and scars in an older woman
Authors: Wang Yuan , Wang Fang , Wu Yongzhuo , Jiang Fuqiong
Published: July 2024

A 71-year-old woman presented with a 30-year history of recurrent fever, fatigue, oral and nasopharyngeal ulcers, facial oedematous erythema and vesicles that ulcerated and healed by forming scars.
Auditory hemispheric asymmetry for actions and objects
Authors: Robert Paul , Zatorre Robert , Gupta Akanksha , Sein Julien , Anton Jean-Luc , Belin Pascal , Thoret Etienne , Morillon Benjamin
Published: July 2024

What is the function of auditory hemispheric asymmetry? We propose that the identification of sound sources relies on the asymmetric processing of two complementary and perceptually relevant acoustic invariants: actions and objects. In a large dataset of environmental sounds, we observed that temporal and spectral modulations display only weak covariation. We then synthesized auditory stimuli by simulating various actions (frictions) occurring on different objects (solid surfaces). Behaviorally, discrimination of actions relies on temporal modulations, while discrimination of objects relies on spectral modulations. Functional magnetic resonance imaging data showed that actions and objects are decoded in the left and right hemispheres, respectively, in bilateral superior temporal and left inferior frontal regions. This asymmetry reflects a generic differential processing—through differential neural sensitivity to temporal and spectral modulations present in environmental sounds—that supports the efficient categorization of actions and objects. These results support an ecologically valid framework of the functional role of auditory brain asymmetry.
Assessing right atrial size in patients with tricuspid regurgitation: importance of the right ventricular-focused view
Authors: Gavazzoni Mara , Badano Luigi P , Pugliesi Giordano Maria , Penso Marco , Hădăreanu Diana-Ruxandra , Ciampi Pellegrino , Fisicaro Samantha , Oliverio Giorgio , Heilbron Francesca , Tomaselli Michele , Muraru Denisa
Published: July 2024

Aims

To assess the accuracy of measuring the right atrial volume (RAV) using two-dimensional echocardiography (2DE) in a right ventricular focused (RVF) view compared to the conventional apical four-chamber (4Ch) view in patients with secondary tricuspid regurgitation (STR). We also compared the clinical correlates of the measures obtained using different methods.

Methods and results

The accuracy of RAV measurements obtained between 2DE-4Ch and RVF views in 384 patients with STR were compared using three-dimensional echocardiography (3DE) as a reference. We used the analysis of variance to test the differences among RAVs obtained from the different 2DE and 3DE acquisitions and the receiving operating characteristics (ROC) curves to evaluate the association with the composite endpoint of hospitalization for heart failure or death. Compared to 3DE, RAV was significantly more underestimated when measurements were obtained from 4Ch rather than RVF (−24 vs. −14%, respectively, P < 0.001 for both). RAV underestimation in 4Ch and RVF view was relatively larger in lower grades of STR (−28 vs. −17% in mild, −23 vs. −14% in moderate, and −19 vs. −11% in severe STR, P = 0.001), and in the atrial compared to ventricular (−28 vs. −22%; P = 0.002) STR. RAV measured by 3DE and RVF showed the highest area under the curve (AUC = 0.67 for 3DE vs. 0.64 for RVF, P = 0.05), while 4Ch was significantly less related to the outcomes (AUC: 0.61, P = 0.021 vs. 3DE RAV).

Conclusion

In patients with STR, the use of RVF view improved the accuracy of 2DE RAV measurement as compared to the conventional 4Ch-derived measurements.
Advances in vaccine development for Chlamydia trachomatis
Authors: Poston Taylor B
Published: July 2024

Chlamydia trachomatis is the most prevalent bacterial sexually transmitted infection globally. Antibiotic treatment is highly effective, but infection is often asymptomatic resulting in most individuals going undetected and untreated. This untreated infection can ascend to the upper female genital tract to cause pelvic inflammatory disease, tubal factor infertility, and ectopic pregnancy. Chlamydia screening and treatment programs have failed to control this epidemic and demonstrate the need for an efficacious vaccine to prevent transmission and disease. Animal models and human epidemiological data reveal that natural immunity can provide partial or short-lived sterilizing immunity. These data further demonstrate the importance of eliciting interferon gamma (IFNγ)-producing cluster of differentiation 4 (CD4) T cells (Th1 and Th1/17 cells) that can likely synergize with antibody-mediated opsonophagocytosis to provide optimal protection. These studies have guided preclinical rational vaccine design for decades and the first Phase 1 clinical trials have recently been completed. Recent advances have led to improvements in vaccine platforms and clinically safe adjuvants that help provide a path forward. This review describes vaccine models, correlates of immunity, antigen and adjuvant selection, and future clinical testing for Chlamydia vaccine development.
Appendix
Authors: Lowenfeld Lea
Published: July 2024

Appendicitis is the most common abdominal pathology in the world. The diagnosis of appendicitis is based on a history of abdominal pain migrating to the right lower quadrant, fevers, and anorexia, a physical examination confirming right lower quadrant tenderness to palpation, leukocytosis, and a computed tomography (CT) scan showing a dilated appendix with surrounding inflammation. Standard treatment of acute uncomplicated appendicitis includes appendectomy, but antibiotic therapy may be considered as an acceptable alternative in select patients. Patients who present with complicated, perforated appendicitis and are unstable or have peritonitis require emergent surgery. Patients with perforated appendicitis who are stable can be treated with antibiotics and drainage of any peri-appendiceal abscesses. For patients treated with non-operative management, interval appendectomy should be considered due to the risk of recurrence, risk of malignancy, and low risk of the operation.
Appendix
Authors: Obeid Lama , Juprasert Jackly , Yeo Heather
Published: July 2024

This chapter discusses tumours of the appendix, which are very rare. Despite their rarity, appendiceal neoplasms have a wide variety of histologic subtypes, each with its own implications on treatment, prognosis, and survival. The two major classifications of appendiceal cancers are neuroendocrine tumours (NET) (previously known as carcinoid tumours) and epithelial tumours, each further divided into various histologic subtypes. Appendiceal tumours are a highly variable group of cancers with widely varying histology and tumour characteristics, which due to their rarity, lends itself to a very difficult diagnostic, prognostic, and treatment evaluation. In addition, over time the classification has changed, as a result management is complex. As more information emerges, both the classification and the treatment pathways illustrated in this chapter are likely to evolve.
The workup of colorectal cancer
Authors: Lu Pamela W. , Fields Adam C. , Melnitchouk Nelya
Published: July 2024

Colorectal cancer is a common disease that all practitioners should have some familiarity with. Despite available guidelines, a proportion of patients do not undergo recommended colorectal cancer screening and can present with complaint of symptoms. Patients with colorectal cancer often have vague or non-specific symptoms such as abdominal pain, change in bowel habits, or rectal bleeding. Workup should begin with a thorough history and physical exam, including a rectal examination. Workup should then be followed up with appropriate diagnostic imaging or procedures if appropriate. Maintaining an index of suspicion when evaluating patients is critical as the epidemiology of colorectal cancer is changing, with rising incidence in patients aged less than 50—prior to the initiation of routine screening.
Ischaemic colitis
Authors: Beresneva Olga , Donohue Kristen , Kleiman David A.
Published: July 2024

Ischaemic colitis is the most common form of intestinal ischaemia. It occurs most often at watershed areas of the colon due to a low-flow state. The gold-standard imaging modality for diagnosis of ischaemic colitis is computerized tomography (CT), along with endoscopy to confirm the radiographic findings. Most patients recover with non-operative management with fluid resuscitation, bowel rest, and antibiotics. Surgical intervention is reserved for progression to full-thickness ischaemia, gangrene, perforation, or failure to improve with non-operative management. Overall mortality is around 13% and significantly higher in those who require surgery. Recurrence also occurs relatively often, in up to 10% of patients. The most common long-term sequelae of ischaemic colitis that may ultimately require surgical correction is the development of a colonic stricture.
Management of colonic volvulus
Authors: Deen Kemal , Ratnatunge Kesara , Deen Raeed
Published: July 2024

Colonic volvulus occurs in segments of colon with a mesentery. Rarely, volvulus may occur in a malrotated caecum. The sigmoid colon is the most frequent site and occurs when the colon rotates upon its axis. Axial rotation greater than 180degrees risks colonic ischaemia and gangrene. Painless gaseous distention of the abdomen is the most common presentation; tenderness is an ominous sign of ischaemia, while computerized tomography is the investigation of choice. Mostly, volvulus affects populations of the Middle East, Africa, and Asia more than in the West. In the former, volvulus is a condition of young people compared with the elderly in the West. Definitive treatment for colonic volvulus is resection and anastomosis while fixation is a temporizing option for those at high surgical risk. Endoscopic decompression of volvulus must be undertaken by an experienced operator and helps reduce ischaemia time but bears the risk of bacteraemia and colonic perforation.
Crohn’s disease
Authors: Mascarenhas Christopher , Kiran Ravi Pokala
Published: July 2024

Crohn’s disease (CD) is a chronic inflammatory condition that involves the entire gastrointestinal tract from the mouth to the anus. The location, pattern, and severity of disease varies between patients. Management is usually medical, with a variety of medications available. Currently a top-down approach to medical management to ensure mucosal healing is considered essential for adequate control and to prevent complications. Despite medical management, a proportion of patients end up needing surgery. When surgery is needed the goals of surgery include conservation of adequate length of small bowel disease over the long-term while adequately controlling disease and managing complications.
Transanal endoscopic microsurgery (TEM), transanal minimally invasive surgery (TAMIS), and transanal total mesorectal excision (TaTME)
Authors: Sali Priyanka A. , Nandakumar Govind
Published: July 2024

This chapter serves as an overview of the recent advances in endoscopic rectal surgery. Various nuances of transanal endoscopic microsurgery (TEM), transanal minimally invasive surgery (TAMIS), transanal total mesorectal excision (TaTME) are discussed. The indications, equipment, technique, complications, functional outcomes, and comparison with other techniques will be dealt with in detail. There are now multiple surgical approaches available as treatment options for rectal cancer, each with specific benefits and drawbacks. The transanal approaches are important tools and appropriate use of these techniques requires training and experience. Transanal approaches are extremely useful in male patients with a narrow pelvis and a low tumour. Each patient and rectal tumour is different and the approach should be individualized to the specific scenario.
Endoluminal surgery in the future
Authors: Nakajima Kiyokazu , Momose Kota
Published: July 2024

This chapter examines how the differences between flexible gastrointestinal (GI) endoscopy and laparoscopic surgery are mostly responsible for the failure of natural orifice transluminal endoscopic surgery (NOTES) and current technical difficulties of endoluminal interventions. A set of new tools will bridge gaps between endoscopy and laparoscopy, and may foster their positive integration towards the next generation endoscopic interventions. The future of GI endoluminal surgery will evolve more rapidly and surely, by developing necessary flexible tools and new systems to bridge the gaps between flexible endoscopy and laparoscopy. Intensive R&D efforts are necessary to accomplish positive integration of ‘two endoscopies’ towards next-generation endoscopic interventions.
SBAs for the MRCOG Part 1
Authors: Karavadra Babu , Haines Richard A. , Sule Medha
Published: July 2024

MRCOG Part 1: 500 SBA’s, contains fresh content to help candidates prepare for this competitive examination. The questions have been carefully written to reflect fundamental areas of the curriculum along with explanations and key references to encourage the candidate to read further. With specific reference to the clinically orientated questions, the answers provide considerations for day-to-day clinical practice; helping the candidate to understand the wider context of their learning. Along with the individual curriculum areas, there are also two sample question papers at the end of the book to help guide further preparation. This is an important resource for anyone preparing for the MRCOG part 1 examination.
Embryology
Authors: Karavadra Babu , Haines Richard A. , Sule Medha
Published: July 2024

This chapter focuses on single best answer questions that test knowledge on basic embryology that is relevant for the MRCOG part 1 examination. Embryology is an important part of the obstetrics and gynaecology curriculum. A good understanding of the basic concepts surrounding fertilisation is important for fetal medicine conditions, as well as early pregnancy considerations including molar pregnancy. Embryology can best be learned by watching videos on the respective processes as well as reading a well written textbook. You should always think about the clinical implications that can result from abnormal embryological development.
Biochemistry
Authors: Karavadra Babu , Haines Richard A. , Sule Medha
Published: July 2024

This chapter focuses on single best answer questions that test knowledge on basic biochemistry that is relevant for the MRCOG part 1 examination. A good understanding of the principles involved in biochemistry will help you to understand various aspects of obstetrics and gynaecology. Examples of applied biochemistry relate to the biochemistry of parturition, signalling pathways in the myometrium and contractility of the myometrium. An understanding of acid-base balance is helpful when understanding physiological changes in labour. Applied biochemistry is often tested when interpreting common investigations within the specialty.
Pathology
Authors: Karavadra Babu , Haines Richard A. , Sule Medha
Published: July 2024

This chapter focuses on single best answer questions that test knowledge on the pathology that is relevant for the MRCOG part 1 examination. An understanding of the basic principles that underpin pathology is important for the practice of obstetrics and gynaecology. An important area where applied pathology is important is within the subspecialty of gynaecological oncology in terms of pre-cancerous lesions, as well as cancer itself. Within the context of obstetrics, the pathological basis of disease must not be underestimated, and the impact should be considered for both the pregnancy individual and her unborn baby. An understanding of normal physiology and anatomy will help to understand pathology further.
Microorganisms and Antibiotics
Authors: Morchi Ravi
Published: July 2024

A summary of essential infectious disease concepts for the surgical resident. It starts with principles of, and definitions within, infection control. Then it reviews classes of microorganisms pertinent to the surgical patient—bacterial, viral, mycobacterial, and fungal. It closes with the mechanisms and targets of commonly utilized antivirals, antibacterials, and antifungals.
Anesthesia and Perioperative Care
Authors: Morchi Ravi
Published: July 2024

A review of clinically relevant hematologic principles for the care of surgical patients. It starts with the coagulation cascade, including the different laboratory measures of coagulative function. Then it covers features of blood product transfusion, transfusion reactions, and medical measures to augment hemostasis. Clinically relevant antiplatelets, anticoagulants, and thrombolytics are described, and commonly tested hypercoagulable states and bleeding disorders are reviewed. The chapter closes with high yield facts on dyshemoglobinemias.
Stomach
Authors: Morchi Ravi
Published: July 2024

A review of the stomach as an organ for capacitance, mixing, and transit, the chapter starts with anatomy and physiology. Important points about esophagogastroduodenoscopy (EGD) and gastrostomy tubes are presented before proceeding to disorders of gastric motility and mucosal inflammation. The diagnosis and management of ulcerative disease includes all classic surgical options and their specific indications. The pathophysiology, diagnosis, and treatment of gastric adenocarcinoma is detailed. Commonly tested post-gastrectomy complications and bariatric surgical procedures are highlighted. The chapter closes with summaries of the less common gastric pathologies, both benign and malignant, that are known to appear on board examinations.
Parathyroid
Authors: Morchi Ravi
Published: July 2024

The anatomy and physiology of parathyroid function is the foundation for this chapter. The clinical approach to hypercalcemia is reviewed. Primary and secondary hyperparathyroidism are detailed, including the differential diagnosis, workup, medical management, and surgical management. High-yield facts regarding operative conduct and complications when pursuing parathyroid pathology are outlined. The chapter closes with parathyroid cancer and multiple endocrine neoplasia syndromes.
Trauma
Authors: Morchi Ravi
Published: July 2024

The presenting principles of traumatic injury and emergency department maneuvers for the moribund patient are presented first. The chapter then reviews the most commonly utilized diagnostic modalities for trauma patients and the indications for emergent and urgent laparotomy. The concepts of damage control surgery and abdominal compartment syndrome are also discussed. The majority of the chapter outlines commonly tested injuries by organ-system, from the brain and spinal cord down through cardiopulmonary, vascular, enteric, hepatosplenic, and urologic. Pelvic, torso soft tissue envelope, and musculoskeletal limb injuries are described last. The chapter closes with a discussion of hypothermia, radiation, and pregnancy.
Neurosurgery and Orthopedics
Authors: Morchi Ravi
Published: July 2024

This chapter is intended to be a high-yield summary of neurosurgery and orthopedics for the general surgery residency board examination. It also serves to familiarize the reader with the terminology and principles of these two fields, to help guide clinical decision-making. Cranial anatomy and physiology is followed by a description of different brain masses, cortical injuries, and spinal cord syndromes and vertebral column trauma. Peripheral nerve pathology ends the section on neurosurgery. For orthopedics, the review starts with bone architecture and principles of fractures. Cervical spine stenosis is followed by brief outlines of upper extremity bony and joint pathology, lumbar spine diseases, and finally bony pelvis and lower extremity musculoskeletal problems. The chapter closes with diabetic extremity gangrene and commonly tested bone tumors.
Neurological complications of myeloid malignancies
Authors: Siegal Tali , Benouaich-Amiel Alexandra , Bairey Osnat
Published: July 2024

Myeloid malignancies are a heterogeneous group of clonal haematopoietic disorders, which include chronic disorders such as chronic myeloid leukaemia, polycythaemia vera, essential thrombocytosis, primary myelofibrosis, myelodysplastic syndromes, and acute disorders such as acute myeloid leukaemias. Accordingly, their neurological manifestations are manifold. Common neurological complications are thrombotic and haemorrhagic events that occur in both acute leukaemias and the more indolent entities. Direct involvement of the nervous system is typically related to acute leukaemias and includes invasion of the central nervous system (parenchymal and leptomeningeal dissemination, myeloid sarcoma, neuroleukaemiosis). Indirect neurological complications derive from cerebrovascular events related to either thrombosis in JAK-2-positive neoplasms or hyperviscosity, or haemorrhage once thrombocythemia or coagulopathy is present. Many neurological complications are iatrogenic and include diverse categories such as lumbar puncture and intrathecal or systemic chemotherapy, targeted therapies, radiotherapy, and allogeneic stem cell transplantation. Most neurological manifestations require urgent treatment and confer a poor prognosis. This chapter describes the neurological complications of myeloid malignancies in the era of contemporary treatment. Those manifestations require expert consideration of their source, as they are being identified with increasing frequency, while patients survive longer.
Neurological complications of medical therapies in haematological malignancies
Authors: Baehring Joachim M. , Soussain Carole
Published: July 2024

Medical therapies, including conventional chemotherapies and newer targeted and immunotherapies, used in haematological malignancies can give rise to a large spectrum of neurological complications either by direct neurotoxicity of the agents or by resulting from intricate effects on cell metabolism, coagulation, the innate and adaptive immune systems, and cerebrospinal fluid (CSF) homeostasis. Multiple drugs used for haematological malignancies can cause central neurotoxicity, manifested by acute or subacute global encephalopathy (busulfan, ifosfamide, intravenous methotrexate, fludarabine), chronic encephalopathy (intravenous methotrexate), a cerebellar syndrome (cytarabine), and aseptic meningitis (intrathecal methotrexate). Peripheral neuropathies are common with vinca alkaloids, proteasome inhibitors, platinum compounds, thalidomide and its analogues, and brentuximab vedotin. Tumour lysis syndrome can manifest with seizures and neuromuscular symptoms. Dural sinus thrombosis is a major risk specific to patients receiving asparaginase. An increasing number of agents have been associated with posterior reversible encephalopathy syndrome. Neuroimmunological complications, initially encountered mainly in the form of haemophagocytic lymphohistiocytosis and central nervous system involvement by graft-versus-host disease after allogeneic stem cell transplantation, are occurring more frequently with the use of immunotherapies, including checkpoint inhibitors, bispecific monoclonal antibodies, and chimeric antigen receptor (CAR) T-cell therapies. The intrinsic risk of opportunistic infections encountered in haematological malignancies is further increased by specific therapeutic interventions, especially haematopoietic stem cell transplantation. Disorders of CSF circulation may occur in patients receiving all-trans retinoic acid. While many of the mechanisms underlying treatment-related neurotoxicities are unknown, haematologists must be aware of these disorders and be able to distinguish them from neurological involvement by the haematological disease itself. Prompt recognition enables the treating multidisciplinary medical team to interrupt the responsible treatment, initiate therapy, and reduce morbidity.
Osteology of the upper limb
Authors: Koshi Rachel
Published: July 2024

Osteology of the upper limb outlines essential knowledge of bones: the clavicle, scapula, humerus, radius, ulna, and hand bones (carpals, metacarpals, and the phalanges). The chapter enables readers to name each bone and determine its position in the body, identify the side to which it belongs, hold it in the anatomical position, describe the important bony features, and demonstrate important muscle attachments on the bone. For each bone the text outlines: General features, Bony landmarks and muscle attachments, unique features, Applied Anatomy and exercises. The chapter outlines the osteology competencies for the upper limb required by the National Medical Council of India curricula.
The back
Authors: Koshi Rachel
Published: July 2024

The back begins with a description of the bony landmarks and surface features of the back. The scapula, vertebral spines, and vertebral levels for surface landmarks are described. The cutaneous nerves supplying the back are discussed. The trapezius, latissimus dorsi, levator scapulae, rhomboid major, and rhomboid minor muscles are described, along with their nerve supply and actions (and the triangle of auscultation is described). Detailed, stepwise instructions are provided to guide the students to dissect the back. The scapular movements are explained, and the origin, insertion, nerve supply, and action of muscles acting on the shoulder girdle and the movements of the shoulder girdle are tabulated. All descriptions and dissections are well illustrated. Results of injury to the long thoracic nerve and the spinal accessory nerve are discussed.
Introduction to the lower limb
Authors: Koshi Rachel
Published: July 2024

This chapter serves as an overview of the lower limb. It lists the different regions of the lower limb—the hip and buttocks, thigh, leg, and foot—and describes the extent of the gluteal region, buttock, inguinal region, thigh, popliteal fossa, leg, and foot. It also describes the main features of the hip bone, bony pelvis, femur, tibia and fibula, tarsal bones, and metatarsal bones. It introduces the term pelvic girdle and illustrates the parts of the girdle on an X-ray. It names the main joints of the lower limb and lists the bones taking part in each.
The front and medial side of the thigh
Authors: Koshi Rachel
Published: July 2024

This chapter describes the bones, muscles, vessels, and nerves in this region. It describes the superficial and deep fasciae, with special attention to the fasciae latae, iliotibial tract, saphenous opening, and cribriform fascia. It traces the long saphenous vein from the foot and describes its termination. It introduces the inguinal ligament and relates it to the femoral canal and important structures in the femoral triangle. It describes the femoral triangle and adductor canal, the quadriceps femoris and other extensor muscles, the adductor muscles, the femoral nerve and obturator nerve, and the femoral artery. It provides detailed, stepwise instructions for dissection of the region. All descriptions and dissections are well illustrated. The clinically important anatomy of the femoral hernia and the patella reflex are described.
The nerves and nerve injuries of the lower limb
Authors: Koshi Rachel
Published: July 2024

This chapter summarizes the sensory and motor distribution of the femoral nerve, obturator nerve, sciatic nerve, tibial nerve, common fibular nerve, deep fibular nerve, medial plantar nerve, and lateral plantar nerve. Information that will help the physician to predict the effects of nerve injury at each level along the course of the nerve is provided in the form of tables. The effect of nerve injury of each of the joints is tabulated, with a description of whether the paralysis would be partial or complete. The sensory distribution and dermatomal pattern of the lower limb are illustrated with diagrams. Peripheral neuropathy of the lower limb is discussed. The standard method for testing the integrity of myotomes L. 2, L. 3, L. 4, L. 5, and S. 1 is shown.
MCQs on the lower limb
Authors: Koshi Rachel
Published: July 2024

The multiple-choice questions provide 15 self-assessment questions to test understanding of the content covered in the chapters on the lower limb. Each question has a single most correct answer from four options given. The questions and answers have been designed to aid revision.
Plasma itraconazole concentrations during treatment of feline sporotrichosis
Authors: Pereira-Oliveira Gabriela Reis , Gremião Isabella Dib Ferreira , Corrêa Maria Lopes , Caroline dos Santos Honorato Cindy , Gonçalves Viana Paula , Figueiredo Anna Barreto Fernandes , Boechat Jéssica Sepúlveda , Guerino dos Reis Érica , Oliveira Raquel de Vasconcelos Carvalhaes , da Silva Aline Campos de Azevedo , Novotny Thiago Santana , Guaraldo Lusiele , Pereira Sandro Antonio
Published: July 2024

Itraconazole (ITZ) is the most used drug to treat feline sporotrichosis; however, little is known about its pharmacokinetics in cats with this mycosis. The aim of this study was to determine plasma ITZ concentrations in cats with sporotrichosis treated with ITZ as monotherapy or in combination with potassium iodide (KI). Cats diagnosed with sporotrichosis received orally ITZ (100 mg/cat/day) or combination therapy with ITZ (100 mg/cat/day) and KI (2.5–5 mg/kg/day) in the case of worsening or stagnation of the clinical condition. At each monthly visit, blood samples were collected at an interval of 4 h for analysis of trough and peak plasma ITZ concentrations by HPLC. Clinical features and laboratory parameters were evaluated during follow-up. Sixteen cats were included in the study. The median plasma ITZ concentration of all cats was 0.75 µg/mL. The median plasma ITZ concentration was 0.5 µg/mL in cats that received ITZ monotherapy (n = 12) and 1.0 µg/mL in those treated with ITZ + KI (n = 4). The clinical cure rate was 56.3% (n = 9) and the median treatment duration was 8 weeks. Nine cats (56.3%) developed adverse clinical reactions, and hyporexia was the most frequent (n = 8; 88.9%). Serum alanine aminotransferase was elevated in four cats (25%). The median plasma ITZ concentration detected in cats was considered to be therapeutic (>0.5 µg/mL) and was reached after 4 weeks of treatment. Plasma ITZ concentrations were higher in cats that received ITZ + KI compared to those treated only with ITZ, suggesting pharmacokinetic synergism between these drugs.
Abscisic acid–mediated autoregulation of the MYB41-BRAHMA module enhances drought tolerance in Arabidopsis
Authors: Gao Lei , Lv Qiang , Wang Lei , Han Shuang , Wang Jing , Chen Yuli , Zhu Wenwen , Zhang Xia , Bao Fang , Hu Yong , Li Ling , He Yikun
Published: July 2024

Drought stress poses a substantial challenge to plant growth and agricultural productivity worldwide. Upon water depletion, plants activate an abscisic acid (ABA) signaling pathway, leading to stomatal closure to reduce water loss. The MYB family of transcription factors plays diverse roles in growth, development, stress responses, and biosynthesis, yet their involvement in stomatal regulation remains unclear. Here, we demonstrate that ABA significantly upregulates the expression of MYB41, MYB74, and MYB102, with MYB41 serving as a key regulator that induces the expression of both MYB74 and MYB102. Through luciferase assays, chromatin immunoprecipitation (ChIP) assays, and electrophoretic mobility shift assays (EMSA), we reveal that MYB41 engages in positive feedback regulation by binding to its own promoter, thus amplifying its transcription in Arabidopsis (Arabidopsis thaliana). Furthermore, our investigation showed that MYB41 recruits BRAHMA (BRM), the core ATPase subunit of the SWI/SNF complex, to the MYB41 promoter, facilitating the binding of HISTONE DEACETYLASE 6 (HDA6). This recruitment triggers epigenetic modifications, resulting in reduced MYB41 expression characterized by elevated H3K27me3 levels and concurrent decreases in H3ac, H3K27ac, and H3K14ac levels in wild-type plants compared to brm knockout mutant plants. Our genetic and molecular analyses show that ABA mediates autoregulation of the MYB41-BRM module, which intricately modulates stomatal movement in A. thaliana. This discovery sheds light on a drought response mechanism with the potential to greatly enhance agricultural productivity.
Can we reach consensus on the dominant sulfate formation pathway in China's haze?
Authors: Liu Mingxu , Song Yu , Wang Tiantian , Dang Xinyi , Shang Fang , Jin Xipeng , Du Mile , Wang Weigang , Sun Yele , Zhang Qiang , Kang Ling , Cai Xuhui , Zhang Hongsheng , Zhu Tong
Published: July 2024

Atmospheric sulfate aerosols contribute significantly to air pollution and climate change. Sulfate formation mechanisms during winter haze events in northern China have recently received considerable attention, with more than 10 studies published in high-impact journals. However, the conclusions from in-field measurements, laboratory studies, and numerical simulations are inconsistent and even contradictory. Here, we propose a physically based yet simple method to clarify the debate on the dominant sulfate formation pathway. Based on the hazes evolving in the synoptic scale, first, a characteristic sulfate formation rate is derived using the Eulerian mass conservation equation constrained by in situ observations. Then, this characteristic value is treated as a guideline to determine the dominant sulfate formation pathway with a 0D chemical box model. Our observation-derived results establish a linkage between studies from laboratory experiments and chemical transport model simulations. A convergent understanding could therefore be reached on sulfate formation mechanisms in China's wintertime haze. This method is universal and can be applied to various haze conditions and different secondary products.
The diffuse interface description of fluid lipid membranes captures key features of the hemifusion pathway and lateral stress profile
Authors: Bottacchiari Matteo , Gallo Mirko , Bussoletti Marco , Casciola Carlo M
Published: July 2024

Topological transitions of lipid membranes are ubiquitous in key biological processes for cell life, like neurotransmission, fertilization, morphogenesis, and viral infections. Despite this, they are not well understood due to their multiscale nature, which limits the use of molecular models and calls for a mesoscopic approach such as the celebrated Canham–Helfrich one. Unfortunately, such a model cannot handle topological transitions, hiding the crucial involved forces and the appearance of the experimentally observed hemifused intermediates. In this work, we describe the membrane as a diffuse interface preserving the Canham–Helfrich elasticity. We show that pivotal features of the hemifusion pathway are captured by this mesoscopic approach, e.g. a (meta)stable hemifusion state and the fusogenic behavior of negative monolayer spontaneous curvatures. The membrane lateral stress profile is calculated as a function of the elastic rigidities, yielding a coarse-grained version of molecular models findings. Insights into the fusogenic mechanism are reported and discussed.
GDF15 regulated by HDAC2 exerts suppressive effects on oxygen–glucose deprivation/reoxygenation-induced neuronal cell pyroptosis via the NLRP3 inflammasome
Authors: Xiao Hua , Chen Wei , Lu Darong , Shi Guixin , Xia Xiangping , Yao Shengtao
Published: July 2024

Background

Pyroptosis, inflammation-related programed cell death mediated by NLRP3 inflammasome, is involved in the pathogenesis of cerebral hypoxic–ischemic injury. Our study aims to explore the biological role of growth differentiation factor (GDF)15 in oxygen–glucose deprivation/reoxygenation (OGD/R)-induced neuronal pyroptosis.

Methods

HT22 neurons were subjected to OGD/R to simulate cerebral hypoxic–ischemic injury. Cells were transfected with plasmids to overexpress GDF15, or lentiviral-based shRNAs constructs to silence GDF15. ELISA assay was used to detect GDF15, IL-1β, IL-18, and neuron specific enolase (NSE) levels. Cell pyroptosis was measured by flow cytometery. Chromatin immunoprecipitation assay was used to detect interaction of H3K27ac with GDF15 promoter. GDF15, NLRP3, Caspase-1 p20 and GSDMD-N expressions were measured by Western blotting.

Results

Patients with malignant middle cerebral artery infarction showed decreased GDF15, but increased IL-1β, IL-18, and NSE levels in serum compared to healthy controls. OGD/R treatment caused significant increases in the levels of IL-1β, IL-18 and NSE, percentages of pyroptotic cells, and expressions of NLRP3, Caspase-1 p20, and GSDMD in HT22 cells, which were markedly reversed by GDF15 overexpression. However, GDF15 knockdown resulted in neuronal injury similar to those observed in OGD/R treatment. The GDF15 knockdown-induced effects were counteracted by treatment with NLRP3 inhibitor. OGD/R decreased the enrichment of H3K27ac in the promoter of GDF15 to down-regulate GDF15, but was compromised by co-treatment with HDAC2 inhibitor.

Conclusion

Our data demonstrates that GDF15 attenuates OGD/R-induced pyroptosis through NLRP3 inflammasome. HDAC2 is involved in mediating OGD-induced GDF15 down-regulation via H3K27ac modification. GDF15 overexpression and HDAC2 inhibition hold potential as useful therapeutic strategies for neuroprotection.
What is causing this patient's urticaria?
Authors: Shamblen Carla
Published: July 2024

This article describes a teenage patient who was referred to a pediatric endocrinologist after her workup for recurring urticaria revealed a suppressed thyroid-stimulating hormone level and positive microsomal thyroid peroxidase antibodies. The patient's laboratory results revealed an autoimmune cause for the urticaria as a result of new-onset autoimmune thyroid disease.
Preferred diuretic therapy for primary hypertension
Authors: Young Trevor D.
Published: July 2024

Because of its greater reduction of major adverse cardiovascular events (MACE), chlorthalidone is recommended over hydrochlorothiazide as the preferred diuretic for patients with primary hypertension. However, hydrochlorothiazide is more commonly prescribed than chlorthalidone for this condition. This article reviews recent studies investigating the effectiveness of chlorthalidone and hydrochlorothiazide in reducing MACE, to help clinicians make an evidence-based informed decision on which diuretic to prescribe.
Experimental Study on the Application of Bioactive Xenogeneic Porcine Cancellous Bone for Cervical Intervertebral Fusion in Goats
Authors: Liang Wenhao , Huang Jinlong , Chen Lingling , Gao Peng , Wu Xiaona , Zhang Tao
Published: July 2024

Study Design:

An experimental study in a cervical intervertebral fusion goat model.

Objective:

To investigate the effect of bioactive xenogeneic porcine cancellous bone applied to the intervertebral fusion of goat cervical vertebrae.

Summary of Background Data:

Although autogenous bone achieves satisfied outcome in cervical intervertebral fusion, it is limited and cause several complications. The application of xenogeneic bone has potential to solve these problems.

Methods:

Thirty local goats were randomly divided into 3 groups: group A (12 goats): autogenous tricortical iliac bone group; group B (6 goats): polyetheretherketone (PEEK) cage with autologous bone; and group C (12 goats): PEEK cage with bioactive xenogeneic porcine cancellous bone. C3–C4 discectomy was performed in each group and the above bone graft and bone graft substitutes were implanted. Lateral cervical spine x-rays were taken at preoperative; immediately postoperative; and 4, 8, 12, and 24 weeks postoperatively every goat. Disc space heights (DSHs) were measured on lateral x-rays. CT examination was performed at 12 and 24 weeks after surgery for the fusion score. After 4 and 8 weeks after surgery, 3 goats were euthanized in both groups A and C to evaluate the immune rejection response through histology. At 12 and 24 weeks after surgery, 3 goats were euthanized in each group. The cervical implants fusion outcome was evaluated through specimen histology observation.

Result:

As time extended, the immune rejection of bioactive xenogeneic porcine cancellous bone gradually subsided. Radiology, specimen observation, and histology manifested that the C3–4 vertebral bodies of goats in each group gradually fused. All the goats in each group achieved bony fusion at 24 weeks after surgery. In terms of preventing intervertebral space collapse, the PEEK cage could achieve better results. There was no significant difference in the remaining experimental data (P>0.05).

Conclusions:

Bioactive xenogeneic porcine cancellous bone can obtain satisfied fusion outcomes in cervical intervertebral fusion and is an ideal intervertebral fusion material in goats.