The Guided Bone Regeneration of a Large, Non-Contained, Perforated Maxillary Anterior Perforation Defect: A Case Report.

The reconstruction of alveolar ridge defects can be challenging, especially when the lesion is large, non-contained, and located in the esthetic region. The present report describes the guided bone regeneration (GBR) procedure and prosthetic rehabilitation of a severe perforation defect in the anterior maxilla. Clinical and radiographic evaluation of the lesion indicated an endodontic-periodontal origin, and biopsy results confirmed the absence of malignancy. GBR was performed with the use of cortical mineralized freeze-dried bone allograft (FDBA) combined with recombinant human platelet derived growth factor BB (rhPDGF-BB) and a resorbable collagen membrane without the use of tenting or fixation screws. At six months post-GBR, cone beam computed tomography (CBCT) revealed adequate bone fill for the placement of 4.1 x 10 mm or 4.1 x 12 mm dental implants. The implant surgery was fully guided with a two-stage approach. After a ten-month of healing phase, the implants were loaded with a screw-retained porcelain bridge. The staged GBR approach using a combination of FDBA, rhPDGF-BB, and a resorbable membrane without the use of tenting or fixation screws resulted in significant bone fill, successful implant placement, and a functional and esthetic implant-supported prosthesis.

Endovascular image-guided sampling of tumor-draining veins provides an enriched source of oncological biomarkers.

Introduction: Circulating tumor-derived biomarkers can potentially impact cancer management throughout the continuum of care. This small exploratory study aimed to assess the relative levels of such biomarkers in the tumor-draining vascular beds in patients with solid tumors compared to levels in their peripheral veins. Methods: Using an endovascular image-guided approach, we obtained blood samples from peripheral veins and other vascular compartments-including the most proximal venous drainage from solid tumors-from a set of nine oncology patients with various primary and metastatic malignancies. We then interrogated these samples for a panel of oncological biomarkers, including circulating tumor cells (CTCs), exosome-derived microRNAs (miRNAs), circulating tumor DNA (ctDNA) mutations, and certain cancer-related proteins/biochemical markers. Results: We found substantially higher levels of CTCs, certain miRNAs, and specific ctDNA mutations in samples from vascular beds closer to the tumor compared with those from peripheral veins and also noted that some of these signals were altered by treatment procedures. Discussion: Our results indicate that tumor-proximal venous samples are highly enriched for some oncological biomarkers and may allow for more robust molecular analysis than peripheral vein samples.

On the brink: The climate and nature crisis and risks of nuclear war

@#The Russian military invasion of Ukraine on February 24, 2022, and Hamas’ terror attack on Israel on October 7, 2023, signaled the beginning of two of the most recent wars to make international headlines. To date, over 110 armed conflicts are taking place: over 45 in the Middle East and North Africa (Cyprus, Egypt, Iraq, Israel, Libya, Morocco, Palestine, Syria, Turkey, Yemen, Western Sahara); over 35 in Africa (Burkina Faso, Cameroon, the Central African Republic, the Democratic Republic of the Congo, Ethiopia, Mali, Mozambique, Nigeria, Senegal, Somalia, South Sudan, Sudan); 21 in Asia (Afghanistan, India, Myanmar, Pakistan, the Philippines); seven in Europe (Russia, Ukraine, Moldova, Georgia, Armenia, Azerbaijan); and six in Latin America (three each in Mexico and Colombia); with two more international armed conflicts (between India and Pakistan, and between India and China) in Asia.1 This list does not even include such problematic situations as those involving China and the South East Asia region. As though these situations of armed violence were not enough, mankind has already passed or is on the verge of passing several climate tipping points – a recent review lists nine Global core tipping elements (and their tipping points) - the Greenland Ice Sheet (collapse); West Antarctic Ice Sheet (collapse); Labrador-Irminger Seas / SPG Convection (collapse); East Antarctic Subglacial Basins (collapse); Amazon Rainforest (dieback); Boreal Permafrost (collapse); Atlantic M.O. Circulation (collapse); Arctic Winter Sea Ice (collapse); and East Antarctic Ice Sheet (collapse); and seven Regional impact tipping elements (and their tipping points) – Low-latitude Coral Reefs (die-off); Boreal Permafrost (abrupt thaw); Barents Sea Ice (abrupt loss); Mountain Glaciers (loss); Sahel and W. African Monsoon (greening); Boreal Forest (southern dieback); and Boreal Forest (northern expansion).2 Closer to home, how can we forget the disaster and devastation wrought by Super Typhoon Haiyan (Yolanda) 10 years ago to date? Whether international or non-international, armed conflicts raise the risk of nuclear war. Russia has already “rehearsed its ability to deliver a ‘massive’ nuclear strike,” conducting “practical launches of ballistic and cruise missiles,” and stationed a first batch of tactical nuclear weapons in Belarus,3 and the possibility of nuclear escalation in Ukraine cannot be overestimated.4 Meanwhile, in a rare public announcement, the U.S. Central Command revealed that an Ohio- class submarine (560 feet long, 18,750 tons submerged and carrying as many as 154 Tomahawk cruise missiles) had arrived in the Middle East on November 5, 2023.5 Indeed, “the danger is great and growing,” as “any use of nuclear weapons would be catastrophic for humanity.”

Association of psychosocial adversity and social information processing in children raised in a low-resource setting: an fNIRS study.

Social cognition skills and socioemotional development are compromised in children growing up in low SES contexts, however, the mechanisms underlying this association remain unknown. Exposure to psychosocial risk factors early in life alters the child's social milieu and in turn, could lead to atypical processing of social stimuli. In this study, we used functional Near Infrared Spectroscopy (fNIRS) to measure cortical responses to a social discrimination task in children raised in a low-resource setting at 6, 24, and 36 months. In addition, we assessed the relation between cortical responses to social and non-social information with psychosocial risk factors assessed using the Childhood Psychosocial Adversity Scale (CPAS). In line with previous findings, we observed specialization to social stimuli in cortical regions in all age groups. In addition, we found that risk factors were associated with social discrimination at 24 months (intimate partner violence and verbal abuse and family conflict) and 36 months (verbal abuse and family conflict and maternal depression) but not at 6 months. Overall, the results show that exposure to psychosocial adversity has more impact on social information processing in toddlerhood than earlier in infancy.

Juvenile morphology of the ornamental crab Mithraculus forceps A. Milne-Edwards, 1875 (Crustacea, Brachyura).

The morphology of juveniles of Mithraculus forceps A. Milne-Edwards, 1875, raised in the laboratory, is described. The larvae were obtained from ovigerous females collected in the wild, maintained in the rearing system for culture of crabs (400 L). A total of 229 larvae (zoea I), from 7 females were distributed in lots of 20 larvae kept in glass flasks (500 ml), with seawater circulation and temperature and salinity constants, which were checked daily for molts or deaths. After the larvae reached the juvenile stage, exuviae and dead specimens were deposited in a scientific collection. We analyzed the external morphology (N = 10 ind.) of each size class (total = 8). We determined the number of size classes, based on carapace width CW vs. carapace length CL (mm) and its dispersion points, in which we can observe non-hierarchical groupings with no size classes overlapping. We analyzed the relative growth of the juveniles using the technique "Standard Major Axis'' (Type II regression). The relationships CW vs. CL and CW vs. AW showed negative allometry (b < 1; p < 0.05). The relationships CW vs. CPH and CW vs. CPL are isometric (b = 1; p > 0.05). The most remarkable morphological characters of the juveniles (first size class) are the following: spines at the anterior margin of the carapace, inner marginal teeth in the propodus and dactylus of the chelipeds, number of articles in the antennular endopod and the maxillular endopod, absence of setae on the maxillar endopod, and absence of rudimentary pleopods.

Two new species of Bimastos (Oligochaeta, Lumbricidae) from the Southern Appalachian Mountains, North America.

Two new species of Bimastos Moore are described based on morphological and molecular data. Bimastos nanae n. sp. resembles B. lawrenceae Fender, B. zeteki (Smith and Gittins) and B. welchi (Smith). Bimastos nanae n. sp. differs from these species in the position of the clitellum, size and number and position of thickened septa. Bimastos magnum n. sp. is similar to B. schwerti Csuzdi Chang and B. palustris Moore in having a fully annular clitellum and male pores on huge porophores. Bimastos magnum n. sp. differs from both species by having a more posterior position of the clitellum (in xxiv-xxxiii, xxxiv) and larger body size. With the description of these new species, the number of Bimastos species is raised to 14.

Management of isolated mandibular body fractures in adults

Objective@#The mandible is the most common fractured craniofacial bone of all craniofacial fractures in the Philippines, with the mandibular body as the most involved segment of all mandibular fractures. To the best of our knowledge, there are no existing guidelines for the diagnosis and management of mandibular body fractures in particular. General guidelines include the American Academy of Otolaryngology – Head and Neck Surgery Foundation (AAOHNSF) Resident Manual of Trauma to the Face, Head, and Neck chapter on Mandibular Trauma, the American Association of Oral and Maxillofacial Surgeons (AAOMS) Clinical Practice Guidelines for Oral and Maxillofacial Surgery section on the Mandibular Angle, Body, and Ramus, and a 2013 Cochrane Systematic Review on interventions for the management of mandibular fractures. On the other hand, a very specific Clinical Practice Guideline on the Management of Unilateral Condylar Fracture of the Mandible was published by the Ministry of Health Malaysia in 2005. Addressing the prevalence of mandibular body fractures, and dearth of specific guidelines for its diagnosis and management, this clinical practice guideline focuses on the management of isolated mandibular body fractures in adults.@*Purpose@#This guideline is meant for all clinicians (otolaryngologists – head and neck surgeons, as well as primary care and specialist physicians, nurses and nurse practitioners, midwives and community health workers, dentists, and emergency first-responders) who may provide care to adults aged 18 years and above that may present with an acute history and physical and/or laboratory examination findings that may lead to a diagnosis of isolated mandibular body fracture and its subsequent medical and surgical management, including health promotion and disease prevention. It is applicable in any setting (including urban and rural primary-care, community centers, treatment units, hospital emergency rooms, operating rooms) in which adults with isolated mandibular body fractures would be identified, diagnosed, or managed. Outcomes are functional resolution of isolated mandibular body fractures; achieving premorbid form; avoiding use of context-inappropriate diagnostics and therapeutics; minimizing use of ineffective interventions; avoiding co-morbid infections, conditions, complications and adverse events; minimizing cost; maximizing health-related quality of life of individuals with isolated mandibular body fracture; increasing patient satisfaction; and preventing recurrence in patients and occurrence in others.@*Action Statements@#The guideline development group made strong recommendationsfor the following key action statements: (6) pain management- clinicians should routinely evaluate pain in patients with isolated mandibular body fractures using a numerical rating scale (NRS) or visual analog scale (VAS); analgesics should be routinely offered to patients with a numerical rating pain scale score or VAS of at least 4/10 (paracetamol and a mild opioid with or without an adjuvant analgesic) until the numerical rating pain scale score or VAS is 3/10 at most; (7) antibiotics- prophylactic antibiotics should be given to adult patients with isolated mandibular body fractures with concomitant mucosal or skin opening with or without direct visualization of bone fragments; penicillin is the drug of choice while clindamycin may be used as an alternative; and (14) prevention- clinicians should advocate for compliance with road traffic safety laws (speed limit, anti-drunk driving, seatbelt and helmet use) for the prevention of motor vehicle, cycling and pedestrian accidents and maxillofacial injuries.The guideline development group made recommendations for the following key action statements: (1) history, clinical presentation, and diagnosis - clinicians should consider a presumptive diagnosis of mandibular fracture in adults presenting with a history of traumatic injury to the jaw plus a positive tongue blade test, and any of the following: malocclusion, trismus, tenderness on jaw closure and broken tooth; (2) panoramic x-ray - clinicians may request for panoramic x-ray as the initial imaging tool in evaluating patients with a presumptive clinical diagnosis; (3) radiographs - where panoramic radiography is not available, clinicians may recommend plain mandibular radiography; (4) computed tomography - if available, non-contrast facial CT Scan may be obtained; (5) immobilization - fractures should be temporarily immobilized/splinted with a figure-of-eight bandage until definitive surgical management can be performed or while initiating transport during emergency situations; (8) anesthesia - nasotracheal intubation is the preferred route of anesthesia; in the presence of contraindications, submental intubation or tracheostomy may be performed; (9) observation - with a soft diet may serve as management for favorable isolated nondisplaced and nonmobile mandibular body fractures with unchanged pre - traumatic occlusion; (10) closed reduction - with immobilization by maxillomandibular fixation for 4-6 weeks may be considered for minimally displaced favorable isolated mandibular body fractures with stable dentition, good nutrition and willingness to comply with post-procedure care that may affect oral hygiene, diet modifications, appearance, oral health and functional concerns (eating, swallowing and speech); (11) open reduction with transosseous wiring - with MMF is an option for isolated displaced unfavorable and unstable mandibular body fracture patients who cannot afford or avail of titanium plates; (12) open reduction with titanium plates - ORIF using titanium plates and screws should be performed in isolated displaced unfavorable and unstable mandibular body fracture; (13) maxillomandibular fixation - intraoperative MMF may not be routinely needed prior to reduction and internal fixation; and (15) promotion - clinicians should play a positive role in the prevention of interpersonal and collective violence as well as the settings in which violence occurs in order to avoid injuries in general and mandibular fractures in particular.

Stochastics of Degradation: The Autophagic-Lysosomal System of the Cell.

Autophagy is a conservative and evolutionarily ancient process that enables the transfer of various cellular compounds, organelles, and potentially dangerous cellular components to the lysosome for their degradation. This process is crucial for the recycling of energy and substrates, which are required for cellular biosynthesis. Autophagy not only plays a major role in the survival of cells under stress conditions, but is also actively involved in maintaining cellular homeostasis. It has multiple effects on the immune system and cellular remodeling during organism development. The effectiveness of autophagy is ensured by a controlled interaction between two organelles - the autophagosome and the lysosome. Despite significant progress in the description of the molecular mechanisms underlying autophagic-lysosomal system (ALS) functioning, many fundamental questions remain. Namely, the specialized functions of lysosomes and the role of ALS in the pathogenesis of human diseases are still enigmatic. Understanding of the mechanisms that are triggered at all stages of autophagic- lysosomal degradation, from the initiation of autophagy to the terminal stage of substrate destruction in the lysosome, may result in new approaches that could help better uderstand ALS and, therefore, selectively control cellular proteostasis.

Otorhinolaryngology Out-Patient Practice in the “Post”-COVID-19 Era: Ensuring a Balance Between Service and Safety

Objective@#To review available resources and provide evidence-based recommendations that may optimize otorhinolaryngologic out-patient health care delivery in the “post”-COVID-19 era while ensuring the safety of our patients, healthcare workers and staff.@*Data Sources@#Relevant peer-reviewed journal articles; task force, organizational and institutional, government and non-government organization recommendations; published guidelines from medical, health-related, and scientific organizations.@*Methods@#A comprehensive review of the literature on the COVID-19 pandemic as it pertained to “post”-COVID 19 out-patient otorhinolaryngologic practice was obtained from peer-reviewed articles, guidelines, recommendations, and statements that were identified through a structured search of the data sources for relevant literature utilizing MEDLINE (through PubMed and PubMed Central PMC), Google (and Google Scholar), HERDIN Plus, the World Health Organization (WHO) Global Health Library, and grey literature including social media (blogs, Twitter, LinkedIn, Facebook). In-patient management (including ORL surgical procedures such as tracheostomy) were excluded. Retrieved material was critically appraised and organized according to five discussion themes: physical office set-up, patient processing, personal protection, procedures, and prevention and health-promotion.@*Conclusion@#These recommendations are consistent with the best available evidence to date, and are globally acceptable while being locally applicable. They address the concerns of otorhinolaryngologists and related specialists about resuming office practice during the “post”-COVID-19 period when strict quarantines are gradually lifted and a transition to the “new” normal is made despite the unavailability of a specific vaccine for SARS-CoV-2. While they target practice settings in the Philippines, they should be useful to ENT (ear, nose & throat) surgeons in other countries in ensuring a balance between service and safety as we continue to serve our patients during these challenging times.

A new species of the genus Microhyla Tschudi, 1838 (Amphibia: Anura: Microhylidae) from Tay Nguyen Plateau, Central Vietnam.

We describe a new species of Microhyla from Tram Lap forest, Gia Lai Province, Central Vietnam based on morphological, molecular, and acoustic data. The new species resembles M. butleri morphologically, but differs from all congeners by a combination of the following morphological attributes: (1) medium-sized adult snout-vent length 25.2-27.0 mm in 15 males and 30.5 mm in a single female; (2) body habitus moderately stocky; (3) head flat, snout rounded, slightly prominent in ventral profile; (4) dorsum and flanks slightly shagreened with evenly scattered tiny tubercles, ventral skin smooth; (5) first finger well developed, more than one-half the length of the second finger; (6) tips of three outer fingers slightly enlarged, forming weak disks and tips of all toes distinctly dilated into wide disks with narrow peripheral grooves; (7) finger and toe disks with dorsal median longitudinal grooves; (8) three palmar tubercles and two metatarsal tubercles; (9) tibiotarsal articulation of adpressed limb reaching slightly beyond the orbit; (10) webbing formula: I 1¾-2 II 1½-2¾ III 2-31/3 IV 3»-1½ V; (11) in life, chin and throat yellowish to bright-orange with tiny dark brown speckling laterally; and (12) a call consisting of 15-26 pulses with a dominant frequency of 1.8-2.2 kHz (recorded at 18.5ºC). We also provide a preliminary genealogy of Microhyla based on analysis of a 2644 bp fragment of 12S-16S rRNA mitochondrial DNA. Based on the examed data, the new species and M. butleri are sister-species (genetic p-distance: 9.0%) and it can be distinguished from M. butleri by its morphology (size, webbing on toes, color) and advertisement call. Interspecific genetic p-distances between the new species and its congeners vary from 9.0% to 14.8%. Microhyla aurantiventris sp. nov. occurs in evergreen montane tropical forests at elevations around 1200 m a.s.l. and is known only from the type locality. The new species appears to be threatened due to intensive logging and agriculture plantation.

Observations on an epilobic Lumbricus rubellus (Oligochaeta, Lumbricidae) from the Great Smoky Mountains National Park, Tennessee, USA.

The genus Lumbricus L. was the first described genus of earthworms, with L. terrestris as its type species. The genus can be easily distinguished because it is the only lumbricid genus with a tanylobic prostomium, with the exception of the North American native Bimastos eiseni (Levinsen). With six known Lumbricus species introduced in North America (Reynolds Wetzel, 2012), Lumbricus rubellus is one of the most widespread. In addition, L. rubellus has been associated with negative ecological effects as result of its invasion (Greiner et al. 2012). The Great Smoky Mountains National Park in Tennessee and North Carolina, USA, is no exception from earthworm invasions (Snyder et al. 2011). Recent research in an area near the extreme southwestern end of the Park (35.5538º N; 83.9943º W), resulted in the collection of ten specimens of L. rubellus, on 27 July 2011. Among these specimens was one that had an abnormal epilobic prostomium and under-developed tubercula pubertatis, whereas the rest had the typical Lumbricus tanylobic prostomia and fully developed tubercula pubertatis. To facilitate discrimination and identification in future encounters of an epilobic L. rubellus we provide here a full description of this specimen. To our knowledge, this is the first reported case of a specimen of L. rubellus with an epilobic prostomium. The specimen will be deposited in the nascent Terrestrial Oligochaete Collection at the Georgia Museum of Natural History in Athens, Georgia, USA. The specimen was fixed in 10% formalin, and is preserved in 70% ethanol.

A new species of Leptolalax (Anura: Megophryidae) from Son Tra Peninsula, central Vietnam.

Morphological, acoustic and molecular analyses result in the description of Leptolalax rowleyae sp. nov., a new species of frog in the Megophryidae, belonging to the L. applebyi Rowley Cao species group from central Vietnam. It differs from its congeners by a combination of the following morphological attributes: (1) adult SVL 23.4-25.4 mm in males and 27-27.8 mm in females; (2) presence of distinct dark/brown dorsolateral markings, including black spots on flanks; (3) pinkish milk-white to light brown chest and belly with numerous white speckles; (4) tympanum distinct; (5) absence of webbing or lateral dermal fringes on fingers and toes; (6) pectoral glands comparatively small (3.3-4.7% of SVL); (7) ventrolateral glands indistinct; and (8) iris bicolored with copper tint in upper half fading to golden in lower third of iris. The male advertisement call of the new species consists of 4-6 notes, lacking a distinct introductory note, with an average dominant frequency of 3.2-3.5 kHz. The description of the tadpole constitutes the first description of larval morphology for a member of the L. appleybi species group. Genetically, an uncorrected sequence divergence of 7.4% for 16S rRNA separates the new species from its two closest relatives, L. ardens and L. melicus in the L. applebyi species group.

A comparative study of pathophysiological alterations in scorpionism induced by Tityus serrulatus and Tityus bahiensis venoms

Scorpionism is a relevant public health problem in several countries in tropical and subtropical regions. In Brazil, Tityus serrulatus sting can induce acute lung injury in part as a consequence of inflammation. Despite the occurrence of other scorpions of Tityus genus in Brazilian scorpiofauna, the knowledge regarding pulmonary alterations is related to T. serrulatus venom (Tsv). Here we studied, comparatively, the pathophysiological changes in the rat airways envenomed by Tsv or T. bahiensis venom (Tbv), since both scorpions are involved in human accidents but with severe envenomations occurring when victims are stung by T. serrulatus. After intravenous injection of the venoms (200 mu g/kg), both were able to induce Evans blue extravasation (in 30 min) into airways and increased protein extravasation into lungs at 4 and 24 h, but the magnitude of such events was higher in Tsv group. Hemorrhage (in 60 min) in the lungs was higher in Tbv group, while IL-1 beta (at 1 h) and IL-6 (at 1 and 4 h) in lung homogenates were detected only in Tsv group. Four and 24 h after envenomation, myeloperoxidase activity in lung was equally augmented in the envenomed groups, as well as an increased in polymorphonuclear cell numbers in bronchoalveolar lavage fluid. At 4 h blood leukogram showed increased leukocyte values with the highest neutrophilia in Tsv group. The numbers of leukocytes and neutrophils remained higher than control at 24 h in Tsv and Tbv groups, and it was accompanied by lympho (envenomed groups) and monocytosis (Tsv group). In conclusion, although Tbv was capable of inducing acute lung injury and blood leukocyte mobilization, most of the evaluated parameters were more affected by the Tsv. These results could help to explain the pathophysiology of the scorpionism and the clinical data arguing toward the greatest severity associated with T. serrulatus stings.

A comparative study of pathophysiological alterations in scorpionism induced by Tityus serrulatus and Tityus bahiensis venoms

Scorpionism is a relevant public health problem in several countries in tropical and subtropical regions. In Brazil, Tityus serrulatus sting can induce acute lung injury in part as a consequence of inflammation. Despite the occurrence of other scorpions of Tityus genus in Brazilian scorpiofauna, the knowledge regarding pulmonary alterations is related to T. serrulatus venom (Tsv). Here we studied, comparatively, the pathophysiological changes in the rat airways envenomed by Tsv or T. bahiensis venom (Tbv), since both scorpions are involved in human accidents but with severe envenomations occurring when victims are stung by T. serrulatus. After intravenous injection of the venoms (200 mu g/kg), both were able to induce Evans blue extravasation (in 30 min) into airways and increased protein extravasation into lungs at 4 and 24 h, but the magnitude of such events was higher in Tsv group. Hemorrhage (in 60 min) in the lungs was higher in Tbv group, while IL-1 beta (at 1 h) and IL-6 (at 1 and 4 h) in lung homogenates were detected only in Tsv group. Four and 24 h after envenomation, myeloperoxidase activity in lung was equally augmented in the envenomed groups, as well as an increased in polymorphonuclear cell numbers in bronchoalveolar lavage fluid. At 4 h blood leukogram showed increased leukocyte values with the highest neutrophilia in Tsv group. The numbers of leukocytes and neutrophils remained higher than control at 24 h in Tsv and Tbv groups, and it was accompanied by lympho (envenomed groups) and monocytosis (Tsv group). In conclusion, although Tbv was capable of inducing acute lung injury and blood leukocyte mobilization, most of the evaluated parameters were more affected by the Tsv. These results could help to explain the pathophysiology of the scorpionism and the clinical data arguing toward the greatest severity associated with T. serrulatus stings.

Death Receptors: New Opportunities in Cancer Therapy.

This article offers a detailed review of the current approaches to anticancer therapy that target the death receptors of malignant cells. Here, we provide a comprehensive overview of the structure and function of death receptors and their ligands, describe the current and latest trends in the development of death receptor agonists, and perform their comparative analysis. In addition, we discuss the DR4 and DR5 agonistic antibodies that are being evaluated at various stages of clinical trials. Finally, we conclude by stating that death receptor agonists may be improved through increasing their stability, solubility, and elimination half-life, as well as by overcoming the resistance of tumor cells. What's more, effective application of these antibodies requires a more detailed study of their use in combination with other anticancer agents.