Similarities and Dissimilarities of COVID-19 and Other Coronavirus Diseases.

In less than two decades, three deadly zoonotic coronaviruses, severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2, have emerged in humans, causing SARS, MERS, and coronavirus disease 2019 (COVID-19), respectively. The current COVID-19 pandemic poses an unprecedented crisis in health care and social and economic development. It reinforces the cruel fact that CoVs are constantly evolving, possessing the genetic malleability to become highly pathogenic in humans. In this review, we start with an overview of CoV diseases and the molecular virology of CoVs, focusing on similarities and differences between SARS-CoV-2 and its highly pathogenic as well as low-pathogenic counterparts. We then discuss mechanisms underlying pathogenesis and virus-host interactions of SARS-CoV-2 and other CoVs, emphasizing the host immune response. Finally, we summarize strategies adopted for the prevention and treatment of CoV diseases and discuss approaches to develop effective antivirals and vaccines.

Variable selection in high dimensions for discrete-outcome individualized treatment rules: Reducing severity of depression symptoms.

Despite growing interest in estimating individualized treatment rules, little attention has been given the binary outcome setting. Estimation is challenging with nonlinear link functions, especially when variable selection is needed. We use a new computational approach to solve a recently proposed doubly robust regularized estimating equation to accomplish this difficult task in a case study of depression treatment. We demonstrate an application of this new approach in combination with a weighted and penalized estimating equation to this challenging binary outcome setting. We demonstrate the double robustness of the method and its effectiveness for variable selection. The work is motivated by and applied to an analysis of treatment for unipolar depression using a population of patients treated at Kaiser Permanente Washington.

The tumor immune microenvironment in resected treatment-naive pancreatic cancer patients with long-term survival.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers worldwide. Presently, only a fraction of patients undergo successful surgical resection, the most effective treatment. Enhancing treatment strategies necessitates a deep comprehension of the factors underlying extended survival after surgical resection in patients. METHODS: This study aims to identify the important factors of PDAC patients' long-term survival with metatranscriptomics and multiplex immunofluorescence (IF) staining analyses. Specifically, differences in tumor immune microenvironment (TIME) were investigated between treatment-naïve PDAC short-term survivors (STS, overall survival <6 months) and long-term survivors (LTS, overall survival >5 years). RESULTS: As a result, we detected 589 over-expressed genes, including HOXB9, CDA, and HOXB8, and 507 under-expressed genes, including AMY2B, SCARA5, and SLC2A2 in LTS. Most of the Reactome overbiological pathways enriched in our data were over-expressed in LTS, such as RHO GTPase Effectors and Cell Cycle Checkpoints. Eleven microbiomes significantly differed between LTS and STS, including Sphingopyxis and Capnocytophaga. Importantly, we demonstrate that the TIME profile with an increased abundance of memory B cells and the reduction of M0 and pro-tumoral M2 macrophages are associated with a good prognosis in PDAC. CONCLUSIONS: In this study, we delved into the TIME with metatranscriptomics and IF staining analyses to understand the prerequisite of prolonged survival in PDAC patients. In LTS, several biological pathways were overexpressed, and specific microbiomes were identified. Furthermore, apparent differences in driven immune factors were found that provide valuable insights into developing new treatment strategies.

Behavioral disorders in multiple sclerosis: a comprehensive review.

Multiple sclerosis (MS) is a heterogenous autoimmune-mediated disease of the central nervous system (CNS) characterized by inflammation, demyelination and chronic progressive neurodegeneration. Among its broad and unpredictable range of neuropsychiatric symptoms, behavioral changes are common, even from the early stages of the disease, while they are associated with cognitive deficits in advanced MS. According to DSM-5, behavioral disorders include attention deficits, oppositional, defiant and conduct disorders, anxiety, panic, obsessive-compulsive disorders (OCD), disruptive and emotional disorders, while others include also irritability, agitation, aggression and executive dysfunctions. Approximately 30 to 80% of individuals with MS demonstrate behavioral changes associated with disease progression. They are often combined with depression and other neuropsychiatric disorders, but usually not correlated with motor deficits, suggesting different pathomechanisms. These and other alterations contribute to disability in MS. While no specific neuropathological data for behavioral changes in MS are available, those in demyelination animal models share similarities with white matter and neuroinflammatory abnormalities in humans. Neuroimaging revealed prefrontal cortical atrophy, interhemispheric inhibition and disruption of fronto-striato-thalamic and frontoparietal networks. This indicates multi-regional patterns of cerebral disturbances within the MS pathology although their pathogenic mechanisms await further elucidation. Benefits of social, psychological, behavioral interventions and exercise were reported. Based on systematical analysis of PubMed, Google Scholar and Cochrane library, current epidemiological, clinical, neuroimaging and pathogenetic evidence are reviewed that may aid early identification of behavioral symptoms in MS, and promote new therapeutic targets and strategies.

Cognitive impairment in multiple sclerosis: from phenomenology to neurobiological mechanisms.

Multiple sclerosis (MS) is an autoimmune-mediated disease of the central nervous system characterized by inflammation, demyelination and chronic progressive neurodegeneration. Among its broad and unpredictable range of clinical symptoms, cognitive impairment (CI) is a common and disabling feature greatly affecting the patients' quality of life. Its prevalence is 20% up to 88% with a wide variety depending on the phenotype of MS, with highest frequency and severity in primary progressive MS. Involving different cognitive domains, CI is often associated with depression and other neuropsychiatric symptoms, but usually not correlated with motor and other deficits, suggesting different pathophysiological mechanisms. While no specific neuropathological data for CI in MS are available, modern research has provided evidence that it arises from the disease-specific brain alterations. Multimodal neuroimaging, besides structural changes of cortical and deep subcortical gray and white matter, exhibited dysfunction of fronto-parietal, thalamo-hippocampal, default mode and cognition-related networks, disruption of inter-network connections and involvement of the γ-aminobutyric acid (GABA) system. This provided a conceptual framework to explain how aberrant pathophysiological processes, including oxidative stress, mitochondrial dysfunction, autoimmune reactions and disruption of essential signaling pathways predict/cause specific disorders of cognition. CI in MS is related to multi-regional patterns of cerebral disturbances, although its complex pathogenic mechanisms await further elucidation. This article, based on systematic analysis of PubMed, Google Scholar and Cochrane Library, reviews current epidemiological, clinical, neuroimaging and pathogenetic evidence that could aid early identification of CI in MS and inform about new therapeutic targets and strategies.

Long non-coding RNAs in cancer: multifaceted roles and potential targets for immunotherapy.

Cancer remains a major global health concern with high mortality rates mainly due to late diagnosis and poor prognosis. Long non-coding RNAs (lncRNAs) are emerging as key regulators of gene expression in human cancer, functioning through various mechanisms including as competing endogenous RNAs (ceRNAs) and indirectly regulating miRNA expression. LncRNAs have been found to have both oncogenic and tumor-suppressive roles in cancer, with the former promoting cancer cell proliferation, migration, invasion, and poor prognosis. Recent research has shown that lncRNAs are expressed in various immune cells and are involved in cancer cell immune escape and the modulation of the tumor microenvironment, thus highlighting their potential as targets for cancer immunotherapy. Targeting lncRNAs in cancer or immune cells could enhance the anti-tumor immune response and improve cancer immunotherapy outcomes. However, further research is required to fully understand the functional roles of lncRNAs in cancer and the immune system and their potential as targets for cancer immunotherapy. This review offers a comprehensive examination of the multifaceted roles of lncRNAs in human cancers, with a focus on their potential as targets for cancer immunotherapy. By exploring the intricate mechanisms underlying lncRNA-mediated regulation of cancer cell proliferation, invasion, and immune evasion, we provide insights into the diverse therapeutic applications of these molecules.

Measured Steps: Navigating the Path of Oligoprogressive Lung Cancer with Targeted and Immunotherapies.

PURPOSE OF REVIEW: This review discusses the definitions, treatment modalities, management, future directions, and ongoing clinical trials of oligoprogressive disease in oncogene-driven and non-oncogene-driven NSCLC. RECENT FINDINGS: During the last decades, diagnostic and treatment modalities for oligometastatic NSCLC have advanced significantly, leading to improved survival. Additionally, our understanding of the tumor biology of oligoprogressive disease has expanded. However, despite the efforts of organizations, such as EORTC, ESTRO, and ASTRO proposing definitions for oligometastatic and oligoprogressive disease, heterogeneity in definitions persists in (ongoing) trials. Recognizing the significance of subclassification within oligoprogressive disease in NSCLC and the varying risks associated with subsequent metastatic spread, there is a call for tailored management strategies. A consensus on standardized criteria for the definition of oligoprogressive disease is urgently needed and will not only facilitate meaningful comparisons between studies but also pave the way for the development of personalized treatment plans that take into account the heterogeneous nature of oligoprogressive disease.

Glucocorticoid efficacy and treatment strategies for drug-induced liver injury: a literature review.

Drug-induced liver injury (DILI) is an adverse reaction to drugs and their metabolites. The activation of adaptive immune and inflammatory responses plays an important role in the pathogenesis of DILI. Glucocorticoids (GCs) have powerful anti-inflammatory and immunosuppressive effects and have been used to treat a variety of immune-mediated liver diseases. Due to the important role of the immune system in DILI, GCs are widely used in the clinical treatment of DILI; however, whether they are beneficial to patients remains controversial. There is no uniform standard for the timing, dosage, and population selection of GCs, which mainly depend on the clinician's experience. Therefore, elucidating whether GCs are beneficial for patients with DILI is an urgent clinical problem. Our review summarizes the recent literature and discusses the clinical efficacy, applicable population, application timing, and efficacy of GCs in special types of DILI, providing a reference for the clinical application of GCs.

Research Progress on Ferroptosis in Multiple Myeloma.

OPINION STATEMENT: Multiple myeloma (MM) is the second most common hematological malignant (HM) tumor, and a large proportion of patients still suffer from treatment failure and a poor prognosis despite the use of some newly approved drugs, a deeper understanding of the underlying mechanism is still needed. Ferroptosis is a new form of programmed cell death (PCD) that is different from other traditional forms of cell death such as apoptosis, necrosis and autophagy. With the continuous deepening of research on ferroptosis, ferroptosis has been found to be closely related to MM. This article reviews the regulatory mechanism of ferroptosis and research progress on ferroptosis in MM, providing a new theoretical basis and strategies for the diagnosis and treatment of MM.

Insights into the removal of antibiotics from livestock and aquaculture wastewater by algae-bacteria symbiosis systems.

With the burgeoning growth of the livestock and aquaculture industries, antibiotic residues in treated wastewater have become a serious ecological threat. Traditional biological wastewater treatment technologies-while effective for removing conventional pollutants, such as organic carbon, ammonia and phosphate-struggle to eliminate emerging contaminants, notably antibiotics. Recently, the use of microalgae has emerged as a sustainable and promising approach for the removal of antibiotics due to their non-target status, rapid growth and carbon recovery capabilities. This review aims to analyse the current state of antibiotic removal from wastewater using algae-bacteria symbiosis systems and provide valuable recommendations for the development of livestock/aquaculture wastewater treatment technologies. It (1) summarises the biological removal mechanisms of typical antibiotics, including bioadsorption, bioaccumulation, biodegradation and co-metabolism; (2) discusses the roles of intracellular regulation, involving extracellular polymeric substances, pigments, antioxidant enzyme systems, signalling molecules and metabolic pathways; (3) analyses the role of treatment facilities in facilitating algae-bacteria symbiosis, such as sequencing batch reactors, stabilisation ponds, membrane bioreactors and bioelectrochemical systems; and (4) provides insights into bottlenecks and potential solutions. This review offers valuable information on the mechanisms and strategies involved in the removal of antibiotics from livestock/aquaculture wastewater through the symbiosis of microalgae and bacteria.

Identifying the optimal treatment strategy in patients with resectable non-cardia gastric cancer.

BACKGROUND: Multimodal treatment strategy including perioperative chemotherapy (PEC), postoperative chemoradiation therapy (POCR), and postoperative chemotherapy (POC) has been accepted as the standard of care in gastric cancer (GC). The ideal sequence and type of therapy remain undetermined. METHOD: The National Cancer Database was examined from 2006 to 2016 to identify patients with resectable non-cardia gastric cancer. Patient outcomes were compared based on the receipt of PEC, POCR, and POC. This comparison was repeated in a sub-group of patients who received optimal treatment. Optimal treatment was defined as initial chemotherapy within 45 days of diagnosis, resection within 45 days of diagnosis, negative margins, adjuvant chemotherapy within 90 days of resection and standard radiation dose (45 Gy). Kaplan-Meier test, log-rank test, and multivariable analysis (MVA) were performed. RESULTS: We identified 9589 patients. Median survival was greater in the PEC group followed by POCR and POC (60.6, 42.3, and 31.2 months, respectively). On MVA, factors associated with worse overall survival included age above median (≥ 63 years), Charlson-Deyo score of ≥ 1, non-academic/research program, poorly differentiated/undifferentiated grade, positive margins, and positive lymph nodes. Both PEC and POCR were associated with improved survival when compared to POC (HR 0.78 and 0.79; p < 0.001). When compared with PEC, no significant difference was noted with POCR (HR 1.01; p = 0.987). These results were maintained in optimally treated cohort (n = 3418). CONCLUSION: In patients with resectable non-cardia gastric cancer, both perioperative chemotherapy and postoperative chemoradiation therapy were associated with improved survival when compared to postoperative chemotherapy. No difference was noted between perioperative chemotherapy and postoperative chemoradiation therapy. These results were maintained in the optimally treated cohort.

Evolution and advances in endovascular mechanical thrombectomy of cerebral venous sinus thrombosis.

Cerebral venous sinus thrombosis (CVST) is a rare type of stroke and standard treatment involves anticoagulation. However, for some special CVST patients who are ineligible for anticoagulation or refractory to conservative treatment, endovascular treatment (EVT) may be an effective option. Mechanical thrombectomy (MT) is a commonly used treatment. Compared with anticoagulation treatment alone, MT may result in additional procedure-related complications, however, many studies have shown that it has a high rate of vessel recanalization and lower incidence of related complications in arterial large vessel occlusion stroke. In addition, the applicability of MT in children, patients with deep cerebral thrombosis, and patients with bleeding before treatment has been reported. MT combined with intravascular thrombolysis (IVT) and other multimodal therapeutic strategies, also has a good curative effect, and further research is needed to compare and optimize different treatment strategies. Owing to the low incidence of CVST, randomized controlled clinical trials with a large sample size to explore the safety and effectiveness of MT are scarce. In addition, devices specifically designed for cerebral venous sinus and effective endovascular therapies are currently not well-established. This article summarizes different endovascular instruments and multimodal therapies for cerebral venous thrombosis. We also discuss the limitations, prospects, prognostic factors, and applications in special cases of interventional thrombectomy.

Risk of metastasis and survival in patients undergoing different treatment strategies with T1 colonic neuroendocrine tumors.

PURPOSE: The efficacy and safety of local excision (LE) for small (< 1‒2 cm) colonic neuroendocrine tumors (NETs) is controversial due to the higher metastasis risk when compared with rectal NETs. The study aimed to evaluate the metastasis risk of T1 colonic NETs and compare patients' long-term prognosis after LE or radical surgery (RS). METHODS: The Surveillance Epidemiology and End Results database was used to identify patients with T1 colonic NETs (2004‒2015). Multivariable logistic regression was performed to assess factors associated with metastasis risk. Propensity score matching was used to balance the variables. Cancer-specific survival (CSS) and overall survival (OS) were calculated to estimate the prognosis of patients with T1N0M0 colonic NETs who underwent LE or RS. RESULTS: Of the 610 patients with colonic NETs, 46 (7.54%) had metastasis at diagnosis. Tumor size (11-20 mm) (OR = 9.51; 95% confidence interval (CI): 4.32‒21.45; P < 0.001), right colon (OR = 15.79; 95% CI 7.20‒38.56; P < 0.001), submucosal infiltration (OR = 2.08; 95% CI 0.84‒5.57; P = 0.125) were independent risk factors associated with metastasis. Of the 515 patients with T1N0M0 colonic NETs, the overall long-term prognosis of LE was as good as that of RS groups (after matching, 5-year CSS: 97.9% vs. 94.6%, P = 0.450; 5-year OS: 92.7% vs. 85.6%, P = 0.009). CONCLUSION: Tumor size (11‒20 mm) and site (right colon) are associated with metastasis in T1 colonic NETs. In the absence of metastasis, LE could be a viable option for 0‒10 mm T1 colonic NETs with well/moderate differentiation in the left colon in terms of long-term survival.

Why do marionette lines appear? Exploring the anatomical perspectives and role of thread-based interventions.

The pathogenesis of marionette lines involves a complex interplay of anatomical, physiological, and age-related factors leading to the development of wrinkles around the oral commissures. This exploration delves into the distinct anatomical predispositions observed among different ethnicities, emphasizing the role of compact modiolus structures and muscle compositions. Notably, individuals of East Asian descent exhibit inherent facial structures that predispose them to pronounced sagging around the oral commissures during aging. The emergence of distinct facial lines, such as the commissural line and the melolabial fold, contributes to the formation of marionette lines. This specific wrinkle pattern, resembling a marionette puppet's mouth contours, is influenced by various factors like bone resorption, gravitational forces, fat compartment variations, muscle compression, ligament tethering, and skin aging. Treatment strategies for marionette lines encompass diverse interventions, including filler injections, botulinum neurotoxin, surgeries targeting fat reduction, thread lifting, and volumizing fillers. These approaches aim to address the underlying causes and mitigate the appearance of marionette lines. Botulinum neurotoxin injections, for instance, weaken specific facial muscles, reducing downward strain and aiding in tissue retraction. Anatomical considerations during procedures are crucial to avoid nerve or vascular damage. Delicate manipulation and precise entry points are essential to prevent inadvertent injuries, particularly concerning blood vessels like the facial artery and nerves like the mental nerve. Technical guidelines for procedures targeting marionette lines involve specific techniques like cogged thread reverse methods and volumizing thread placements. Attention to entry points, tissue engagement, and the direction of threads is crucial for effective treatment outcomes, minimizing complications, and ensuring patient safety.

Sunitinib resistance in renal cell carcinoma: From molecular mechanisms to predictive biomarkers.

Currently, renal cell carcinoma (RCC) is the most prevalent type of kidney cancer. Targeted therapy has replaced radiation therapy and chemotherapy as the main treatment option for RCC due to the lack of significant efficacy with these conventional therapeutic regimens. Sunitinib, a drug used to treat gastrointestinal tumors and renal cell carcinoma, inhibits the tyrosine kinase activity of a number of receptor tyrosine kinases, including vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), c-Kit, rearranged during transfection (RET) and fms-related receptor tyrosine kinase 3 (Flt3). Although sunitinib has been shown to be efficacious in the treatment of patients with advanced RCC, a significant number of patients have primary resistance to sunitinib or acquired drug resistance within the 6-15 months of therapy. Thus, in order to develop more efficacious and long-lasting treatment strategies for patients with advanced RCC, it will be crucial to ascertain how to overcome sunitinib resistance that is produced by various drug resistance mechanisms. In this review, we discuss: 1) molecular mechanisms of sunitinib resistance; 2) strategies to overcome sunitinib resistance and 3) potential predictive biomarkers of sunitinib resistance.

A retrospective clinical analysis of 11 cases of PEComa from different sites.

PURPOSE: The objective of this paper is to offer a thorough examination of the clinical presentations, etiology, and treatment strategies associated with perivascular epithelioid cell tumors (PEComas). METHODS: This retrospective study examined the comprehensive archival data of PEComa cases diagnosed at Beijing Hospital from 2015 to 2023. The pathology slides of all patients were thoroughly reassessed by two experienced pathologists. A thorough retrospective analysis was undertaken, incorporating clinicopathological data including gender, age at diagnosis, initial clinical manifestations, signs, disease onset site, tumor markers, imaging findings, therapeutic modalities, pathological features, immunohistochemical profiles, treatment responses, and prognostic indicators. Patients were evaluated for disease severity according to established pathological classification criteria and were followed up until the designated analysis cut-off date. In instances where patients were unable to be monitored on-site, they were contacted via telephone for postoperative follow-up inquiries. RESULTS: This study included 11 patients with ages ranging from 17 to 66 years old, presenting with the disease in multiple anatomical sites, including the retroperitoneum (2/11), liver (4/11), kidney (4/11), lung (1/11), and broad ligament of the uterus (1/11). Most patients presented with non-specific clinical symptoms and were subsequently diagnosed with space-occupying lesions upon physical examination. The tumor demonstrated progressive growth and enlargement, which could result in compression of neighboring organs. Preoperative imaging alone is insufficient for a definitive diagnosis of PEComa, but MRI can provide an initial evaluation of the tumor's potential malignancy. Molecular marker testing specific to PEComa, such as HMB-45 (90.0%), SMA (81.8%), Melan-A (90.9%), vimentin (90.9%), and Desmin (36.3%), was conducted on all patients. No adjuvant therapies were administered postoperatively. Upon analysis, no instances of relapse at the primary site or the development of new tumors at other sites were observed. Regular imaging reviews of three patients with malignant PEComa post-surgery showed no evidence of recurrence. CONCLUSIONS: The clinical presentation, tumor biomarkers, and imaging characteristics of PEComa lack specificity, necessitating dependence on pathology and immunohistochemistry for precise diagnosis. The mainstay of treatment consists of surgical resection, with patients typically experiencing a favorable prognosis.

Treatment strategies for simple elbow dislocation - a systematic review.

BACKGROUND: Current treatment concepts for simple elbow dislocation involve conservative and surgical approaches. The aim of this systematic review was to identify the superiority of one treatment strategy over the other by a qualitative analysis in adult patients who suffered simple elbow luxation. STUDY DESIGN: A systematic review in accordance with the PRISMA guidelines and following the suggestions for reporting on qualitative summaries was performed. A literature search was conducted using PubMed and Scopus, including variations and combinations of the following keywords: elbow, radiohumeral, ulnohumeral, radioulnar, luxation, and therapy. Seventeen studies that performed a randomized controlled trial to compare treatment strategies as conservative or surgical procedures were included. Reviews are not selected for further qualitative analysis. The following outcome parameters were compared: range of motion (ROM), Mayo Elbow Performance Score (MEPS), Disabilities of the Arm, Shoulder and Hand outcome measure (Quick-DASH), recurrent instability, pain measured by visual analog scale (VAS) and time to return to work (RW). RESULTS: Early mobilization after conservative treatment strategies showed improved ROM compared to immobilization for up to 3 weeks after surgery with less extension deficit in the early mobilization group (16° ± 13°. vs. 19.5° ± 3°, p < 0.05), as well as excellent clinical outcome scores. Surgical approaches showed similar results compared to conservative treatment, leading to improved ROM (115 vs. 118 ± 2.8) and MEPS: 95 ± 7 vs. 92 ± 4. CONCLUSION: Conservative treatment with early functional training of the elbow remains the first-line therapy for simple elbow dislocation. The surgical procedure provides similar outcomes compared to conservative treatment regarding MEPS and ROM for patients with slight initial instability in physical examination and radiographs. People with red flags for persistent instability, such as severe bilateral ligament injuries and moderate to severe instability during initial physical examination, should be considered for a primary surgical approach to prevent recurrent posterolateral and valgus instability. Postoperative early mobilization and early mobilization for conservatively treated patients is beneficial to improve patient outcome and ROM.

Focus on Mitochondrial Respiratory Chain: Potential Therapeutic Target for Chronic Renal Failure.

The function of the respiratory chain is closely associated with kidney function, and the dysfunction of the respiratory chain is a primary pathophysiological change in chronic kidney failure. The incidence of chronic kidney failure caused by defects in respiratory-chain-related genes has frequently been overlooked. Correcting abnormal metabolic reprogramming, rescuing the "toxic respiratory chain", and targeting the clearance of mitochondrial reactive oxygen species are potential therapies for treating chronic kidney failure. These treatments have shown promising results in slowing fibrosis and inflammation progression and improving kidney function in various animal models of chronic kidney failure and patients with chronic kidney disease (CKD). The mitochondrial respiratory chain is a key target worthy of attention in the treatment of chronic kidney failure. This review integrated research related to the mitochondrial respiratory chain and chronic kidney failure, primarily elucidating the pathological status of the mitochondrial respiratory chain in chronic kidney failure and potential therapeutic drugs. It provided new ideas for the treatment of kidney failure and promoted the development of drugs targeting the mitochondrial respiratory chain.

Insights into Intra Periodontal Pocket Pathogenesis, Treatment, In Vitro-In Vivo Models, Products and Patents, Challenges and Opportunity.

Periodontal disease is a multifactorial pathogenic condition involving microbial infection, inflammation, and various systemic complications. Here, a systematic and comprehensive review discussing key-points such as the pros and cons of conventional methods, new advancements, challenges, patents and products, and future prospects is presented. A systematic review process was adopted here by using the following keywords: periodontal diseases, pathogenesis, models, patents, challenges, recent developments, and 3-D printing scaffolds. Search engines used were "google scholar", "web of science", "scopus", and "pubmed", along with textbooks published over the last few decades. A thorough study of the published data rendered an accurate and deep understanding of periodontal diseases, the gap of research so far, and future opportunities. Formulation scientists and doctors need to be interconnected for a better understanding of the disease to prescribe a quality product. Moreover, prime challenges (such as a lack of a vital testing model, scarcity of clinical and preclinical data, products allowing for high drug access to deeper tissue regions for prolonged residence, lack of an international monitoring body, lack of 4D or time controlled scaffolds, and lack of successful AI based tools) exist that must be addressed for designing new quality products. Generally, several products have been commercialized to treat periodontal diseases with certain limitations. Various strategic approaches have been attempted to target certain delivery regions, maximize residence time, improve efficacy, and reduce toxicity. Conclusively, the current review summarizes valuable information for researchers and healthcare professional to treat a wide range of periodontal diseases.

[Rehabilitative strategies in cancer-related fatigue]. / Rehabilitationsstrategien bei tumorassoziierter Fatigue.

Cancer-related fatigue (CRF) during and after tumor therapy influences all aspects of life and lowers performance and quality of life. Regular CRF screening and diagnostic evaluation are important factors in the care of patients. This article presents strategies for recognizing and treating CRF. Multiprofessional and personalized therapies can improve CRF. Outpatient and inpatient rehabilitative strategies should be implemented after completion of tumor therapy.